251 results on '"Yuzaki M"'
Search Results
2. Cbln and C1q family proteins – New transneuronal cytokines
- Author
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Yuzaki, M.
- Published
- 2008
- Full Text
- View/download PDF
3. The complement family complements synapses in the central nervous system: S10–04
- Author
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Yuzaki, M., Watanabe, M., Okabe, S., and Sakimura, K.
- Published
- 2013
4. Characterization of the apoptosis-associated tyrosine kinase (AATYK) expressed in the CNS
- Author
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Tomomura, M, Fernandez-Gonzales, A, Yano, R, and Yuzaki, M
- Published
- 2001
- Full Text
- View/download PDF
5. A novel ALS/FTD model mouse expressing cytoplasmic mutant FUS leads neurodegeneration via dendritic homeostasis disruption
- Author
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Shiihashi, G., primary, Ito, D., additional, Arai, I., additional, Kobayashi, Y., additional, Hayashi, K., additional, Otsuka, S., additional, Nakajima, K., additional, Yuzaki, M., additional, Itohara, S., additional, and Suzuki, N., additional
- Published
- 2017
- Full Text
- View/download PDF
6. Guidelines for the use and interpretation of assays for monitoring autophagy
- Author
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Klionsky, D.J. Abdalla, F.C. Abeliovich, H. Abraham, R.T. Acevedo-Arozena, A. Adeli, K. Agholme, L. Agnello, M. Agostinis, P. Aguirre-Ghiso, J.A. Ahn, H.J. Ait-Mohamed, O. Ait-Si-Ali, S. Akematsu, T. Akira, S. Al-Younes, H.M. Al-Zeer, M.A. Albert, M.L. Albin, R.L. Alegre-Abarrategui, J. Aleo, M.F. Alirezaei, M. Almasan, A. Almonte-Becerril, M. Amano, A. Amaravadi, R. Amarnath, S. Amer, A.O. Andrieu-Abadie, N. Anantharam, V. Ann, D.K. Anoopkumar-Dukie, S. Aoki, H. Apostolova, N. Arancia, G. Aris, J.P. Asanuma, K. Asare, N.Y.O. Ashida, H. Askanas, V. Askew, D.S. Auberger, P. Baba, M. Backues, S.K. Baehrecke, E.H. Bahr, B.A. Bai, X.-Y. Bailly, Y. Baiocchi, R. Baldini, G. Balduini, W. Ballabio, A. Bamber, B.A. Bampton, E.T.W. Bánhegyi, G. Bartholomew, C.R. Bassham, D.C. Bast Jr., R.C. Batoko, H. Bay, B.-H. Beau, I. Béchet, D.M. Begley, T.J. Behl, C. Behrends, C. Bekri, S. Bellaire, B. Bendall, L.J. Benetti, L. Berliocchi, L. Bernardi, H. Bernassola, F. Besteiro, S. Bhatia-Kissova, I. Bi, X. Biard-Piechaczyk, M. Blum, J.S. Boise, L.H. Bonaldo, P. Boone, D.L. Bornhauser, B.C. Bortoluci, K.R. Bossis, I. Bost, F. Bourquin, J.-P. Boya, P. Boyer-Guittaut, M. Bozhkov, P.V. Brady, N.R. Brancolini, C. Brech, A. Brenman, J.E. Brennand, A. Bresnick, E.H. Brest, P. Bridges, D. Bristol, M.L. Brookes, P.S. Brown, E.J. Brumell, J.H. Brunetti-Pierri, N. Brunk, U.T. Bulman, D.E. Bultman, S.J. Bultynck, G. Burbulla, L.F. Bursch, W. Butchar, J.P. Buzgariu, W. Bydlowski, S.P. Cadwell, K. Cahová, M. Cai, D. Cai, J. Cai, Q. Calabretta, B. Calvo-Garrido, J. Camougrand, N. Campanella, M. Campos-Salinas, J. Candi, E. Cao, L. Caplan, A.B. Carding, S.R. Cardoso, S.M. Carew, J.S. Carlin, C.R. Carmignac, V. Carneiro, L.A.M. Carra, S. Caruso, R.A. Casari, G. Casas, C. Castino, R. Cebollero, E. Cecconi, F. Celli, J. Chaachouay, H. Chae, H.-J. Chai, C.-Y. Chan, D.C. Chan, E.Y. Chang, R.C.-C. Che, C.-M. Chen, C.-C. Chen, G.-C. Chen, G.-Q. Chen, M. Chen, Q. Chen, S.S.-L. Chen, W. Chen, X. Chen, X. Chen, X. Chen, Y.-G. Chen, Y. Chen, Y. Chen, Y.-J. Chen, Z. Cheng, A. Cheng, C.H.K. Cheng, Y. Cheong, H. Cheong, J.-H. Cherry, S. Chess-Williams, R. Cheung, Z.H. Chevet, E. Chiang, H.-L. Chiarelli, R. Chiba, T. Chin, L.-S. Chiou, S.-H. Chisari, F.V. Cho, C.H. Cho, D.-H. Choi, A.M.K. Choi, D. Choi, K.S. Choi, M.E. Chouaib, S. Choubey, D. Choubey, V. Chu, C.T. Chuang, T.-H. Chueh, S.-H. Chun, T. Chwae, Y.-J. Chye, M.-L. Ciarcia, R. Ciriolo, M.R. Clague, M.J. Clark, R.S.B. Clarke, P.G.H. Clarke, R. Codogno, P. Coller, H.A. Colombo, M.I. Comincini, S. Condello, M. Condorelli, F. Cookson, M.R. Coombs, G.H. Coppens, I. Corbalan, R. Cossart, P. Costelli, P. Costes, S. Coto-Montes, A. Couve, E. Coxon, F.P. Cregg, J.M. Crespo, J.L. Cronjé, M.J. Cuervo, A.M. Cullen, J.J. Czaja, M.J. D'Amelio, M. Darfeuille-Michaud, A. Davids, L.M. Davies, F.E. De Felici, M. De Groot, J.F. De Haan, C.A.M. De Martino, L. De Milito, A. De Tata, V. Debnath, J. Degterev, A. Dehay, B. Delbridge, L.M.D. Demarchi, F. Deng, Y.Z. Dengjel, J. Dent, P. Denton, D. Deretic, V. Desai, S.D. Devenish, R.J. Di Gioacchino, M. Di Paolo, G. Di Pietro, C. Díaz-Araya, G. Díaz-Laviada, I. Diaz-Meco, M.T. Diaz-Nido, J. Dikic, I. Dinesh-Kumar, S.P. Ding, W.-X. Distelhorst, C.W. Diwan, A. Djavaheri-Mergny, M. Dokudovskaya, S. Dong, Z. Dorsey, F.C. Dosenko, V. Dowling, J.J. Doxsey, S. Dreux, M. Drew, M.E. Duan, Q. Duchosal, M.A. Duff, K. Dugail, I. Durbeej, M. Duszenko, M. Edelstein, C.L. Edinger, A.L. Egea, G. Eichinger, L. Eissa, N.T. Ekmekcioglu, S. El-Deiry, W.S. Elazar, Z. Elgendy, M. Ellerby, L.M. Er Eng, K. Engelbrecht, A.-M. Engelender, S. Erenpreisa, J. Escalante, R. Esclatine, A. Eskelinen, E.-L. Espert, L. Espina, V. Fan, H. Fan, J. Fan, Q.-W. Fan, Z. Fang, S. Fang, Y. Fanto, M. Fanzani, A. Farkas, T. Farré, J.-C. Faure, M. Fechheimer, M. Feng, C.G. Feng, J. Feng, Q. Feng, Y. Fésüs, L. Feuer, R. Figueiredo-Pereira, M.E. Fimia, G.M. Fingar, D.C. Finkbeiner, S. Finkel, T. Finley, K.D. Fiorito, F. Fisher, E.A. Fisher, P.B. Flajolet, M. Florez-McClure, M.L. Florio, S. Fon, E.A. Fornai, F. Fortunato, F. Fotedar, R. Fowler, D.H. Fox, H.S. Franco, R. Frankel, L.B. Fransen, M. Fuentes, J.M. Fueyo, J. Fujii, J. Fujisaki, K. Fujita, E. Fukuda, M. Furukawa, R.H. Gaestel, M. Gailly, P. Gajewska, M. Galliot, B. Galy, V. Ganesh, S. Ganetzky, B. Ganley, I.G. Gao, F.-B. Gao, G.F. Gao, J. Garcia, L. Garcia-Manero, G. Garcia-Marcos, M. Garmyn, M. Gartel, A.L. Gatti, E. Gautel, M. Gawriluk, T.R. Gegg, M.E. Geng, J. Germain, M. Gestwicki, J.E. Gewirtz, D.A. Ghavami, S. Ghosh, P. Giammarioli, A.M. Giatromanolaki, A.N. Gibson, S.B. Gilkerson, R.W. Ginger, M.L. Ginsberg, H.N. Golab, J. Goligorsky, M.S. Golstein, P. Gomez-Manzano, C. Goncu, E. Gongora, C. Gonzalez, C.D. Gonzalez, R. González-Estévez, C. González-Polo, R.A. Gonzalez-Rey, E. Gorbunov, N.V. Gorski, S. Goruppi, S. Gottlieb, R.A. Gozuacik, D. Granato, G.E. Grant, G.D. Green, K.N. Gregorc, A. Gros, F. Grose, C. Grunt, T.W. Gual, P. Guan, J.-L. Guan, K.-L. Guichard, S.M. Gukovskaya, A.S. Gukovsky, I. Gunst, J. Gustafsson, A.B. Halayko, A.J. Hale, A.N. Halonen, S.K. Hamasaki, M. Han, F. Han, T. Hancock, M.K. Hansen, M. Harada, H. Harada, M. Hardt, S.E. Harper, J.W. Harris, A.L. Harris, J. Harris, S.D. Hashimoto, M. Haspel, J.A. Hayashi, S.-I. Hazelhurst, L.A. He, C. He, Y.-W. Hébert, M.-J. Heidenreich, K.A. Helfrich, M.H. Helgason, G.V. Henske, E.P. Herman, B. Herman, P.K. Hetz, C. Hilfiker, S. Hill, J.A. Hocking, L.J. Hofman, P. Hofmann, T.G. Höhfeld, J. Holyoake, T.L. Hong, M.-H. Hood, D.A. Hotamisligil, G.S. Houwerzijl, E.J. Høyer-Hansen, M. Hu, B. Hu, C.-A.A. Hu, H.-M. Hua, Y. Huang, C. Huang, J. Huang, S. Huang, W.-P. Huber, T.B. Huh, W.-K. Hung, T.-H. Hupp, T.R. Hur, G.M. Hurley, J.B. Hussain, S.N.A. Hussey, P.J. Hwang, J.J. Hwang, S. Ichihara, A. Ilkhanizadeh, S. Inoki, K. Into, T. Iovane, V. Iovanna, J.L. Ip, N.Y. Isaka, Y. Ishida, H. Isidoro, C. Isobe, K.-I. Iwasaki, A. Izquierdo, M. Izumi, Y. Jaakkola, P.M. Jäättelä, M. Jackson, G.R. Jackson, W.T. Janji, B. Jendrach, M. Jeon, J.-H. Jeung, E.-B. Jiang, H. Jiang, H. Jiang, J.X. Jiang, M. Jiang, Q. Jiang, X. Jiménez, A. Jin, M. Jin, S. Joe, C.O. Johansen, T. Johnson, D.E. Johnson, G.V.W. Jones, N.L. Joseph, B. Joseph, S.K. Joubert, A.M. Juhász, G. Juillerat-Jeanneret, L. Jung, C.H. Jung, Y.-K. Kaarniranta, K. Kaasik, A. Kabuta, T. Kadowaki, M. Kagedal, K. Kamada, Y. Kaminskyy, V.O. Kampinga, H.H. Kanamori, H. Kang, C. Kang, K.B. Il Kang, K. Kang, R. Kang, Y.-A. Kanki, T. Kanneganti, T.-D. Kanno, H. Kanthasamy, A.G. Kanthasamy, A. Karantza, V. Kaushal, G.P. Kaushik, S. Kawazoe, Y. Ke, P.-Y. Kehrl, J.H. Kelekar, A. Kerkhoff, C. Kessel, D.H. Khalil, H. Kiel, J.A.K.W. Kiger, A.A. Kihara, A. Kim, D.R. Kim, D.-H. Kim, D.-H. Kim, E.-K. Kim, H.-R. Kim, J.-S. Kim, J.H. Kim, J.C. Kim, J.K. Kim, P.K. Kim, S.W. Kim, Y.-S. Kim, Y. Kimchi, A. Kimmelman, A.C. King, J.S. Kinsella, T.J. Kirkin, V. Kirshenbaum, L.A. Kitamoto, K. Kitazato, K. Klein, L. Klimecki, W.T. Klucken, J. Knecht, E. Ko, B.C.B. Koch, J.C. Koga, H. Koh, J.-Y. Koh, Y.H. Koike, M. Komatsu, M. Kominami, E. Kong, H.J. Kong, W.-J. Korolchuk, V.I. Kotake, Y. Koukourakis, M.I. Kouri Flores, J.B. Kovács, A.L. Kraft, C. Krainc, D. Krämer, H. Kretz-Remy, C. Krichevsky, A.M. Kroemer, G. Krüger, R. Krut, O. Ktistakis, N.T. Kuan, C.-Y. Kucharczyk, R. Kumar, A. Kumar, R. Kumar, S. Kundu, M. Kung, H.-J. Kurz, T. Kwon, H.J. La Spada, A.R. Lafont, F. Lamark, T. Landry, J. Lane, J.D. Lapaquette, P. Laporte, J.F. László, L. Lavandero, S. Lavoie, J.N. Layfield, R. Lazo, P.A. Le, W. Le Cam, L. Ledbetter, D.J. Lee, A.J.X. Lee, B.-W. Lee, G.M. Lee, J. Lee, J.-H. Lee, M. Lee, M.-S. Lee, S.H. Leeuwenburgh, C. Legembre, P. Legouis, R. Lehmann, M. Lei, H.-Y. Lei, Q.-Y. Leib, D.A. Leiro, J. Lemasters, J.J. Lemoine, A. Lesniak, M.S. Lev, D. Levenson, V.V. Levine, B. Levy, E. Li, F. Li, J.-L. Li, L. Li, S. Li, W. Li, X.-J. Li, Y.-B. Li, Y.-P. Liang, C. Liang, Q. Liao, Y.-F. Liberski, P.P. Lieberman, A. Lim, H.J. Lim, K.-L. Lim, K. Lin, C.-F. Lin, F.-C. Lin, J. Lin, J.D. Lin, K. Lin, W.-W. Lin, W.-C. Lin, Y.-L. Linden, R. Lingor, P. Lippincott-Schwartz, J. Lisanti, M.P. Liton, P.B. Liu, B. Liu, C.-F. Liu, K. Liu, L. Liu, Q.A. Liu, W. Liu, Y.-C. Liu, Y. Lockshin, R.A. Lok, C.-N. Lonial, S. Loos, B. Lopez-Berestein, G. López-Otín, C. Lossi, L. Lotze, M.T. Lõw, P. Lu, B. Lu, B. Lu, B. Lu, Z. Luciano, F. Lukacs, N.W. Lund, A.H. Lynch-Day, M.A. Ma, Y. Macian, F. MacKeigan, J.P. Macleod, K.F. Madeo, F. Maiuri, L. Maiuri, M.C. Malagoli, D. Malicdan, M.C.V. Malorni, W. Man, N. Mandelkow, E.-M. Manon, S. Manov, I. Mao, K. Mao, X. Mao, Z. Marambaud, P. Marazziti, D. Marcel, Y.L. Marchbank, K. Marchetti, P. Marciniak, S.J. Marcondes, M. Mardi, M. Marfe, G. Mariño, G. Markaki, M. Marten, M.R. Martin, S.J. Martinand-Mari, C. Martinet, W. Martinez-Vicente, M. Masini, M. Matarrese, P. Matsuo, S. Matteoni, R. Mayer, A. Mazure, N.M. McConkey, D.J. McConnell, M.J. McDermott, C. McDonald, C. McInerney, G.M. McKenna, S.L. McLaughlin, B. McLean, P.J. McMaster, C.R. McQuibban, G.A. Meijer, A.J. Meisler, M.H. Meléndez, A. Melia, T.J. Melino, G. Mena, M.A. Menendez, J.A. Menna-Barreto, R.F.S. Menon, M.B. Menzies, F.M. Mercer, C.A. Merighi, A. Merry, D.E. Meschini, S. Meyer, C.G. Meyer, T.F. Miao, C.-Y. Miao, J.-Y. Michels, P.A.M. Michiels, C. Mijaljica, D. Milojkovic, A. Minucci, S. Miracco, C. Miranti, C.K. Mitroulis, I. Miyazawa, K. Mizushima, N. Mograbi, B. Mohseni, S. Molero, X. Mollereau, B. Mollinedo, F. Momoi, T. Monastyrska, I. Monick, M.M. Monteiro, M.J. Moore, M.N. Mora, R. Moreau, K. Moreira, P.I. Moriyasu, Y. Moscat, J. Mostowy, S. Mottram, J.C. Motyl, T. Moussa, C.E.-H. Müller, S. Muller, S. Münger, K. Münz, C. Murphy, L.O. Murphy, M.E. Musarò, A. Mysorekar, I. Nagata, E. Nagata, K. Nahimana, A. Nair, U. Nakagawa, T. Nakahira, K. Nakano, H. Nakatogawa, H. Nanjundan, M. Naqvi, N.I. Narendra, D.P. Narita, M. Navarro, M. Nawrocki, S.T. Nazarko, T.Y. Nemchenko, A. Netea, M.G. Neufeld, T.P. Ney, P.A. Nezis, I.P. Nguyen, H.P. Nie, D. Nishino, I. Nislow, C. Nixon, R.A. Noda, T. Noegel, A.A. Nogalska, A. Noguchi, S. Notterpek, L. Novak, I. Nozaki, T. Nukina, N. Nürnberger, T. Nyfeler, B. Obara, K. Oberley, T.D. Oddo, S. Ogawa, M. Ohashi, T. Okamoto, K. Oleinick, N.L. Oliver, F.J. Olsen, L.J. Olsson, S. Opota, O. Osborne, T.F. Ostrander, G.K. Otsu, K. Ou, J.-H.J. Ouimet, M. Overholtzer, M. Ozpolat, B. Paganetti, P. Pagnini, U. Pallet, N. Palmer, G.E. Palumbo, C. Pan, T. Panaretakis, T. Pandey, U.B. Papackova, Z. Papassideri, I. Paris, I. Park, J. Park, O.K. Parys, J.B. Parzych, K.R. Patschan, S. Patterson, C. Pattingre, S. Pawelek, J.M. Peng, J. Perlmutter, D.H. Perrotta, I. Perry, G. Pervaiz, S. Peter, M. Peters, G.J. Petersen, M. Petrovski, G. Phang, J.M. Piacentini, M. Pierre, P. Pierrefite-Carle, V. Pierron, G. Pinkas-Kramarski, R. Piras, A. Piri, N. Platanias, L.C. Pöggeler, S. Poirot, M. Poletti, A. Poüs, C. Pozuelo-Rubio, M. Prætorius-Ibba, M. Prasad, A. Prescott, M. Priault, M. Produit-Zengaffinen, N. Progulske-Fox, A. Proikas-Cezanne, T. Przedborski, S. Przyklenk, K. Puertollano, R. Puyal, J. Qian, S.-B. Qin, L. Qin, Z.-H. Quaggin, S.E. Raben, N. Rabinowich, H. Rabkin, S.W. Rahman, I. Rami, A. Ramm, G. Randall, G. Randow, F. Rao, V.A. Rathmell, J.C. Ravikumar, B. Ray, S.K. Reed, B.H. Reed, J.C. Reggiori, F. Régnier-Vigouroux, A. Reichert, A.S. Reiners Jr., J.J. Reiter, R.J. Ren, J. Revuelta, J.L. Rhodes, C.J. Ritis, K. Rizzo, E. Robbins, J. Roberge, M. Roca, H. Roccheri, M.C. Rocchi, S. Rodemann, H.P. De Córdoba, S.R. Rohrer, B. Roninson, I.B. Rosen, K. Rost-Roszkowska, M.M. Rouis, M. Rouschop, K.M.A. Rovetta, F. Rubin, B.P. Rubinsztein, D.C. Ruckdeschel, K. Rucker III, E.B. Rudich, A. Rudolf, E. Ruiz-Opazo, N. Russo, R. Rusten, T.E. Ryan, K.M. Ryter, S.W. Sabatini, D.M. Sadoshima, J. Saha, T. Saitoh, T. Sakagami, H. Sakai, Y. Salekdeh, G.H. Salomoni, P. Salvaterra, P.M. Salvesen, G. Salvioli, R. Sanchez, A.M.J. Sánchez-Alcázar, J.A. Sánchez-Prieto, R. Sandri, M. Sankar, U. Sansanwal, P. Santambrogio, L. Saran, S. Sarkar, S. Sarwal, M. Sasakawa, C. Sasnauskiene, A. Sass, M. Sato, K. Sato, M. Schapira, A.H.V. Scharl, M. Schätzl, H.M. Scheper, W. Schiaffino, S. Schneider, C. Schneider, M.E. Schneider-Stock, R. Schoenlein, P.V. Schorderet, D.F. Schüller, C. Schwartz, G.K. Scorrano, L. Sealy, L. Seglen, P.O. Segura-Aguilar, J. Seiliez, I. Seleverstov, O. Sell, C. Seo, J.B. Separovic, D. Setaluri, V. Setoguchi, T. Settembre, C. Shacka, J.J. Shanmugam, M. Shapiro, I.M. Shaulian, E. Shaw, R.J. Shelhamer, J.H. Shen, H.-M. Shen, W.-C. Sheng, Z.-H. Shi, Y. Shibuya, K. Shidoji, Y. Shieh, J.-J. Shih, C.-M. Shimada, Y. Shimizu, S. Shintani, T. Shirihai, O.S. Shore, G.C. Sibirny, A.A. Sidhu, S.B. Sikorska, B. Silva-Zacarin, E.C.M. Simmons, A. Simon, A.K. Simon, H.-U. Simone, C. Simonsen, A. Sinclair, D.A. Singh, R. Sinha, D. Sinicrope, F.A. Sirko, A. Siu, P.M. Sivridis, E. Skop, V. Skulachev, V.P. Slack, R.S. Smaili, S.S. Smith, D.R. Soengas, M.S. Soldati, T. Song, X. Sood, A.K. Soong, T.W. Sotgia, F. Spector, S.A. Spies, C.D. Springer, W. Srinivasula, S.M. Stefanis, L. Steffan, J.S. Stendel, R. Stenmark, H. Stephanou, A. Stern, S.T. Sternberg, C. Stork, B. Strålfors, P. Subauste, C.S. Sui, X. Sulzer, D. Sun, J. Sun, S.-Y. Sun, Z.-J. Sung, J.J.Y. Suzuki, K. Suzuki, T. Swanson, M.S. Swanton, C. Sweeney, S.T. Sy, L.-K. Szabadkai, G. Tabas, I. Taegtmeyer, H. Tafani, M. Takács-Vellai, K. Takano, Y. Takegawa, K. Takemura, G. Takeshita, F. Talbot, N.J. Tan, K.S.W. Tanaka, K. Tanaka, K. Tang, D. Tang, D. Tanida, I. Tannous, B.A. Tavernarakis, N. Taylor, G.S. Taylor, G.A. Taylor, J.P. Terada, A.S. Terman, A. Tettamanti, G. Thevissen, K. Thompson, C.B. Thorburn, A. Thumm, M. Tian, F. Tian, Y. Tocchini-Valentini, G. Tolkovsky, A.M. Tomino, Y. Tönges, L. Tooze, S.A. Tournier, C. Tower, J. Towns, R. Trajkovic, V. Travassos, L.H. Tsai, T.-F. Tschan, M.P. Tsubata, T. Tsung, A. Turk, B. Turner, L.S. Tyagi, S.C. Uchiyama, Y. Ueno, T. Umekawa, M. Umemiya-Shirafuji, R. Unni, V.K. Vaccaro, M.I. Valente, E.M. Van Den Berghe, G. Van Der Klei, I.J. Van Doorn, W.G. Van Dyk, L.F. Van Egmond, M. Van Grunsven, L.A. Vandenabeele, P. Vandenberghe, W.P. Vanhorebeek, I. Vaquero, E.C. Velasco, G. Vellai, T. Vicencio, J.M. Vierstra, R.D. Vila, M. Vindis, C. Viola, G. Viscomi, M.T. Voitsekhovskaja, O.V. Von Haefen, C. Votruba, M. Wada, K. Wade-Martins, R. Walker, C.L. Walsh, C.M. Walter, J. Wan, X.-B. Wang, A. Wang, C. Wang, D. Wang, F. Wang, F. Wang, G. Wang, H. Wang, H.-G. Wang, H.-D. Wang, J. Wang, K. Wang, M. Wang, R.C. Wang, X. Wang, X. Wang, Y.-J. Wang, Y. Wang, Z. Wang, Z.C. Wang, Z. Wansink, D.G. Ward, D.M. Watada, H. Waters, S.L. Webster, P. Wei, L. Weihl, C.C. Weiss, W.A. Welford, S.M. Wen, L.-P. Whitehouse, C.A. Whitton, J.L. Whitworth, A.J. Wileman, T. Wiley, J.W. Wilkinson, S. Willbold, D. Williams, R.L. Williamson, P.R. Wouters, B.G. Wu, C. Wu, D.-C. Wu, W.K.K. Wyttenbach, A. Xavier, R.J. Xi, Z. Xia, P. Xiao, G. Xie, Z. Xie, Z. Xu, D.-Z. Xu, J. Xu, L. Xu, X. Yamamoto, A. Yamamoto, A. Yamashina, S. Yamashita, M. Yan, X. Yanagida, M. Yang, D.-S. Yang, E. Yang, J.-M. Yang, S.Y. Yang, W. Yang, W.Y. Yang, Z. Yao, M.-C. Yao, T.-P. Yeganeh, B. Yen, W.-L. Yin, J.-J. Yin, X.-M. Yoo, O.-J. Yoon, G. Yoon, S.-Y. Yorimitsu, T. Yoshikawa, Y. Yoshimori, T. Yoshimoto, K. You, H.J. Youle, R.J. Younes, A. Yu, L. Yu, L. Yu, S.-W. Yu, W.H. Yuan, Z.-M. Yue, Z. Yun, C.-H. Yuzaki, M. Zabirnyk, O. Silva-Zacarin, E. David Zacks, E. Zacksenhaus, L. Zaffaroni, N. Zakeri, Z. Zeh III, H.J. Zeitlin, S.O. Zhang, H. Zhang, H.-L. Zhang, J. Zhang, J.-P. Zhang, L. Zhang, L. Zhang, M.-Y. Zhang, X.D. Zhao, M. Zhao, Y.-F. Zhao, Y. Zhao, Z.J. Zheng, X. Zhivotovsky, B. Zhong, Q. Zhou, C.-Z. Zhu, C. Zhu, W.-G. Zhu, X.-F. Zhu, X. Zhu, Y. Zoladek, T. Zong, W.-X. Zorzano, A. Zschocke, J. Zuckerbraun, B.
- Abstract
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field. © 2012 Landes Bioscience.
- Published
- 2012
7. ROR Regulates Multiple Aspects of Dendrite Development in Cerebellar Purkinje Cells In Vivo
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Takeo, Y. H., primary, Kakegawa, W., additional, Miura, E., additional, and Yuzaki, M., additional
- Published
- 2015
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8. Crystal structure of mouse C1QL1 globular domain
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Kakegawa, W., primary, Mitakidis, N., additional, Miura, E., additional, Abe, M., additional, Matsuda, K., additional, Takeo, Y., additional, Kohda, K., additional, Motohashi, J., additional, Takahashi, A., additional, Nagao, S., additional, Muramatsu, S., additional, Watanabe, M., additional, Sakimura, K., additional, Aricescu, A.R., additional, and Yuzaki, M., additional
- Published
- 2015
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9. CAPS1 Deficiency Perturbs Dense-Core Vesicle Trafficking and Golgi Structure and Reduces Presynaptic Release Probability in the Mouse Brain
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Sadakata, T., primary, Kakegawa, W., additional, Shinoda, Y., additional, Hosono, M., additional, Katoh-Semba, R., additional, Sekine, Y., additional, Sato, Y., additional, Tanaka, M., additional, Iwasato, T., additional, Itohara, S., additional, Furuyama, K., additional, Kawaguchi, Y., additional, Ishizaki, Y., additional, Yuzaki, M., additional, and Furuichi, T., additional
- Published
- 2013
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10. Reevaluation of Neurodegeneration in lurcher Mice: Constitutive Ion Fluxes Cause Cell Death with, Not by, Autophagy
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Nishiyama, J., primary, Matsuda, K., additional, Kakegawa, W., additional, Yamada, N., additional, Motohashi, J., additional, Mizushima, N., additional, and Yuzaki, M., additional
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- 2010
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11. New (but old) molecules regulating synapse integrity and plasticity: Cbln1 and the δ2 glutamate receptor
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Yuzaki, M., primary
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- 2009
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12. The N-Terminal Domain of GluD2 (GluR 2) Recruits Presynaptic Terminals and Regulates Synaptogenesis in the Cerebellum In Vivo
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Kakegawa, W., primary, Miyazaki, T., additional, Kohda, K., additional, Matsuda, K., additional, Emi, K., additional, Motohashi, J., additional, Watanabe, M., additional, and Yuzaki, M., additional
- Published
- 2009
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13. Activity-Dependent Repression of Cbln1 Expression: Mechanism for Developmental and Homeostatic Regulation of Synapses in the Cerebellum
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Iijima, T., primary, Emi, K., additional, and Yuzaki, M., additional
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- 2009
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14. Cbln1 Regulates Rapid Formation and Maintenance of Excitatory Synapses in Mature Cerebellar Purkinje Cells In Vitro and In Vivo
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Ito-Ishida, A., primary, Miura, E., additional, Emi, K., additional, Matsuda, K., additional, Iijima, T., additional, Kondo, T., additional, Kohda, K., additional, Watanabe, M., additional, and Yuzaki, M., additional
- Published
- 2008
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15. Impaired Cerebellar Development and Function in Mice Lacking CAPS2, a Protein Involved in Neurotrophin Release
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Sadakata, T., primary, Kakegawa, W., additional, Mizoguchi, A., additional, Washida, M., additional, Katoh-Semba, R., additional, Shutoh, F., additional, Okamoto, T., additional, Nakashima, H., additional, Kimura, K., additional, Tanaka, M., additional, Sekine, Y., additional, Itohara, S., additional, Yuzaki, M., additional, Nagao, S., additional, and Furuichi, T., additional
- Published
- 2007
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- View/download PDF
16. A study on hot-carrier-induced photoemission in n-MOSFETs under dynamic operation.
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Ohzone, T., Yuzaki, M., Matsuda, T., and Kameda, E.
- Published
- 2000
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17. A stimulus paradigm inducing long-term desensitization of AMPA receptors evokes a specific increase in BDNF mRNA in cerebellar slices.
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Yuzaki, M, primary, Furuichi, T, additional, Mikoshiba, K, additional, and Kagawa, Y, additional
- Published
- 1994
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- View/download PDF
18. Identification of MOS oxide defect location with a spatial resolution less than 0.1 /spl mu/m using photoemission microscope.
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Ohzone, T., Yuzaki, M., Matsuda, T., and Kameda, E.
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- 1999
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19. Characterization of Metabotropic Glutamate Receptors in Cultured Purkinje Cells
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YUZAKI, M., primary, MIKOSHIBA, K., additional, and KAGAWA, Y., additional
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- 1993
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20. Cerebellar Astrocytes Specifically Support the Survival of Purkinje Cells in Culture
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Yuzaki, M., primary, Mikoshiba, K., additional, and Kagawa, Y., additional
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- 1993
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- View/download PDF
21. Pharmacological and immunocytochemical characterization of metabotropic glutamate receptors in cultured Purkinje cells
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Yuzaki, M, primary and Mikoshiba, K, additional
- Published
- 1992
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22. Molecular cloning and characterization of the inositol 1,4,5-trisphosphate receptor in Drosophila melanogaster.
- Author
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Yoshikawa, S, primary, Tanimura, T, additional, Miyawaki, A, additional, Nakamura, M, additional, Yuzaki, M, additional, Furuichi, T, additional, and Mikoshiba, K, additional
- Published
- 1992
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23. An additional form of rat Bcl-x, Bcl-xbeta, generated by an unspliced RNA, promotes apoptosis in promyeloid cells.
- Author
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Shiraiwa, N, Inohara, N, Okada, S, Yuzaki, M, Shoji, S, and Ohta, S
- Abstract
The bcl-2 oncogene product delays apoptotic cell death and prolongs the cell survival. We cloned two bcl-2-related cDNAs from a rat thymus cDNA library by low stringency hybridization with a rat bcl-2 fragment as a probe. One of these, designated bcl-xalpha, was a counterpart of the human bcl-xL reported previously as a bcl-2-related gene (Boise, L. H., Gonzalez-Garcia, M., Postema, C. E. , Ding, L., Lindsten, T., Turka, L. A., Mao, M., Nunez, G., and Thompson, C. B. (1993) Cell 74, 597-608). The other, designated bcl-xbeta, was novel and found to be generated by an unspliced mRNA, whereas bcl-xalpha was generated from a spliced transcript. The splice junction exactly corresponded to that found in the bcl-2 gene. bcl-xbeta was specifically expressed in cerebellum, heart, and thymus. When bcl-xbeta directed by a strong promoter was introduced into an interleukin-3-dependent promyeloid cell line, FDC-P1, DNA fragmentation was observed even in the growing state in the presence of interleukin-3 although not in the control transfectants. This finding suggests that the rat bcl-xbeta gene product promotes apoptosis in the promyeloid cells.
- Published
- 1996
24. Aberrant membranes and double-membrane structures accumulate in the axons of Atg5-null Purkinje cells before neuronal death
- Author
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Nishiyama, J., Miura, E., Noboru Mizushima, Watanabe, M., and Yuzaki, M.
25. A study on hot-carrier-induced photoemission in n-MOSFETs under dynamic operation
- Author
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Ohzone, T., primary, Yuzaki, M., additional, Matsuda, T., additional, and Kameda, E., additional
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- View/download PDF
26. Ortner syndrome associated with aortic pseudoaneurysm after repair of aortic coarctation 30 years previously.
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Fukunaga N, Koyama T, Konishi Y, Murashita T, Yuzaki M, Shomura Y, Fujiwara H, Okada Y, Fukunaga, Naoto, Koyama, Tadaaki, Konishi, Yasunobu, Murashita, Takashi, Yuzaki, Mitsuru, Shomura, Yu, Fujiwara, Hiroshi, and Okada, Yukikatsu
- Published
- 2012
- Full Text
- View/download PDF
27. Lack of evidence for direct ligand-gated ion channel activity of GluD receptors.
- Author
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Itoh M, Piot L, Mony L, Paoletti P, and Yuzaki M
- Subjects
- Animals, Humans, Mice, Glycine metabolism, HEK293 Cells, Ligand-Gated Ion Channels metabolism, Ligand-Gated Ion Channels genetics, Ligands, Serine metabolism, Ion Channel Gating drug effects, Receptors, Glutamate metabolism
- Abstract
Delta receptors (GluD1 and GluD2), members of the large ionotropic glutamate receptor (iGluR) family, play a central role in numerous neurodevelopmental and psychiatric disorders. The amino-terminal domain (ATD) of GluD orchestrates synapse formation and maturation processes through its interaction with the Cbln family of synaptic organizers and neurexin (Nrxn). The transsynaptic triad of Nrxn-Cbln-GluD also serves as a potent regulator of synaptic plasticity, at both excitatory and inhibitory synapses. Despite these recognized functions, there is still debate as to whether GluD functions as a "canonical" ion channel, similar to other iGluRs. A recent report proposes that the ATD of GluD2 imposes conformational constraints on channel activity; removal of this constraint by binding to Cbln1 and Nrxn, or removal of the ATD, reveals channel activity in GluD2 upon administration of glycine (Gly) and d-serine (d-Ser), two GluD ligands. We were able to reproduce currents when Gly or d-Ser was administered to clusters of heterologous human embryonic kidney 293 (HEK293) cells expressing Cbln1, GluD2 (or GluD1), and Nrxn. However, Gly or d-Ser, but also l-glutamate (l-Glu), evoked similar currents in naive (i.e., untransfected) HEK293 cells and in GluD2-null Purkinje neurons. Furthermore, no current was detected in isolated HEK293 cells expressing GluD2 lacking the ATD upon administration of Gly. Taken together, these results cast doubt on the previously proposed hypothesis that extracellular ligands directly gate wild-type GluD channels., Competing Interests: Competing interests statement:The authors declare no competing interest.
- Published
- 2024
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- View/download PDF
28. Kainate receptors regulate synaptic integrity and plasticity by forming a complex with synaptic organizers in the cerebellum.
- Author
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Kakegawa W, Paternain AV, Matsuda K, Aller MI, Iida I, Miura E, Nozawa K, Yamasaki T, Sakimura K, Yuzaki M, and Lerma J
- Abstract
Kainate (KA)-type glutamate receptors (KARs) are implicated in various neuropsychiatric and neurological disorders through their ionotropic and metabotropic actions. However, compared to AMPA- and NMDA-type receptor functions, many aspects of KAR biology remain incompletely understood. Our study demonstrates an important role of KARs in organizing climbing fiber (CF)-Purkinje cell (PC) synapses and synaptic plasticity in the cerebellum, independently of their ion channel or metabotropic functions. The amino-terminal domain (ATD) of the GluK4 KAR subunit binds to C1ql1, provided by CFs, and associates with Bai3, an adhesion-type G protein-coupled receptor expressed in PC dendrites. Mice lacking GluK4 exhibit no KAR-mediated responses, reduced C1ql1 and Bai3 levels, and fewer CF-PC synapses, along with impaired long-term depression and oculomotor learning. Remarkably, introduction of the ATD of GluK4 significantly improves all these phenotypes. These findings demonstrate that KARs act as synaptic scaffolds, orchestrating synapses by forming a KAR-C1ql1-Bai3 complex in the cerebellum., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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29. Correction: Calsyntenin-3 interacts with both α- and β-neurexins in the regulation of excitatory synaptic innervation in specific schaffer collateral pathways.
- Author
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Kim H, Kim D, Kim J, Lee HY, Park D, Kang H, Matsuda K, Sterky FH, Yuzaki M, Kim JY, Choi SY, Ko J, and Um JW
- Published
- 2024
- Full Text
- View/download PDF
30. Abundant extrasynaptic expression of α3β4-containing nicotinic acetylcholine receptors in the medial habenula-interpeduncular nucleus pathway in mice.
- Author
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Tsuzuki A, Yamasaki M, Konno K, Miyazaki T, Takei N, Tomita S, Yuzaki M, and Watanabe M
- Subjects
- Animals, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neurons metabolism, Synapses metabolism, Habenula metabolism, Interpeduncular Nucleus metabolism, Receptors, Nicotinic metabolism, Receptors, Nicotinic genetics
- Abstract
Nicotinic acetylcholine receptors (nAChRs) in the medial habenula (MHb)-interpeduncular nucleus (IPN) pathway play critical roles in nicotine-related behaviors. This pathway is particularly enriched in nAChR α3 and β4 subunits, both of which are genetically linked to nicotine dependence. However, the cellular and subcellular expression of endogenous α3β4-containing nAChRs remains largely unknown because specific antibodies and appropriate detection methods were unavailable. Here, we successfully uncovered the expression of endogenous nAChRs containing α3 and β4 subunits in the MHb-IPN pathway using novel specific antibodies and a fixative glyoxal that enables simultaneous detection of synaptic and extrasynaptic molecules. Immunofluorescence and immunoelectron microscopy revealed that both subunits were predominantly localized to the extrasynaptic cell surface of somatodendritic and axonal compartments of MHb neurons but not at their synaptic junctions. Immunolabeling for α3 and β4 subunits disappeared in α5β4-knockout brains, which we used as negative controls. The enriched and diffuse extrasynaptic expression along the MHb-IPN pathway suggests that α3β4-containing nAChRs may enhance the excitability of MHb neurons and neurotransmitter release from their presynaptic terminals in the IPN. The revealed distribution pattern provides a molecular and anatomical basis for understanding the functional role of α3β4-containing nAChRs in the crucial pathway of nicotine dependence., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
31. The hidden face of GluD1 at inhibitory synapses.
- Author
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Itoh M and Yuzaki M
- Subjects
- Animals, Humans, Receptors, AMPA metabolism, Synapses metabolism
- Published
- 2024
- Full Text
- View/download PDF
32. Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants for Japanese Patients With Venous Thromboembolism - The Primary Results From the KUROSIO Study.
- Author
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Yamada N, Tamaru S, Umetsu M, Tsujita K, Nakamura M, Watanabe A, Yuzaki M, Nishimura Y, Ogura T, Yamamoto T, Satokawa H, Obayashi T, and Nakamura M
- Abstract
Background: Direct oral anticoagulants (DOACs) are recommended as the first-choice anticoagulation therapy in the acute phase of venous thromboembolism (VTE). However, there is limited real-world data for Japanese VTE patients.Methods and Results: The KUROSIO study (UMIN000023747) was a prospective long-term observational study comprising 1,017 patients with concurrent acute symptomatic pulmonary thromboembolism and proximal deep vein thrombosis (DVT) or isolated calf DVT initially treated with DOACs. After excluding 24 patients, 993 (mean age, 66.3±15.1 years; 58.6% females) were analyzed. The incidences of recurrent symptomatic VTE and major bleeding for up to 52 weeks after diagnosis were 3.2% and 2.2%, respectively. Multivariate analyses revealed chemotherapy and anemia as significant risk factors associated with recurrent symptomatic VTE and major bleeding, respectively., Conclusions: The efficacy and safety of DOACs in Japanese patients with VTE were determined in this real-world observational study.
- Published
- 2024
- Full Text
- View/download PDF
33. Activity-driven synaptic translocation of LGI1 controls excitatory neurotransmission.
- Author
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Cuhadar U, Calzado-Reyes L, Pascual-Caro C, Aberra AS, Ritzau-Jost A, Aggarwal A, Ibata K, Podgorski K, Yuzaki M, Geis C, Hallerman S, Hoppa MB, and de Juan-Sanz J
- Subjects
- Humans, Animals, Mice, Glutamic Acid metabolism, Protein Transport, Male, ADAM Proteins metabolism, Neurons metabolism, Autoantibodies immunology, Mice, Inbred C57BL, Synaptic Transmission physiology, Synapses metabolism, Intracellular Signaling Peptides and Proteins metabolism
- Abstract
The fine control of synaptic function requires robust trans-synaptic molecular interactions. However, it remains poorly understood how trans-synaptic bridges change to reflect the functional states of the synapse. Here, we develop optical tools to visualize in firing synapses the molecular behavior of two trans-synaptic proteins, LGI1 and ADAM23, and find that neuronal activity acutely rearranges their abundance at the synaptic cleft. Surprisingly, synaptic LGI1 is primarily not secreted, as described elsewhere, but exo- and endocytosed through its interaction with ADAM23. Activity-driven translocation of LGI1 facilitates the formation of trans-synaptic connections proportionally to the history of activity of the synapse, adjusting excitatory transmission to synaptic firing rates. Accordingly, we find that patient-derived autoantibodies against LGI1 reduce its surface fraction and cause increased glutamate release. Our findings suggest that LGI1 abundance at the synaptic cleft can be acutely remodeled and serves as a critical control point for synaptic function., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
34. Human-induced pluripotent stem cell-derived neural stem/progenitor cell ex vivo gene therapy with synaptic organizer CPTX for spinal cord injury.
- Author
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Saijo Y, Nagoshi N, Kawai M, Kitagawa T, Suematsu Y, Ozaki M, Shinozaki M, Kohyama J, Shibata S, Takeuchi K, Nakamura M, Yuzaki M, and Okano H
- Subjects
- Humans, Rats, Animals, Cell Differentiation genetics, Stem Cell Transplantation, Spinal Cord, Genetic Therapy, Recovery of Function physiology, Induced Pluripotent Stem Cells pathology, Spinal Cord Injuries genetics, Spinal Cord Injuries therapy, Spinal Cord Injuries pathology
- Abstract
The transplantation of neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) has shown promise in spinal cord injury (SCI) model animals. Establishing a functional synaptic connection between the transplanted and host neurons is crucial for motor function recovery. To boost therapeutic outcomes, we developed an ex vivo gene therapy aimed at promoting synapse formation by expressing the synthetic excitatory synapse organizer CPTX in hiPSC-NS/PCs. Using an immunocompromised transgenic rat model of SCI, we evaluated the effects of transplanting CPTX-expressing hiPSC-NS/PCs using histological and functional analyses. Our findings revealed a significant increase in excitatory synapse formation at the transplantation site. Retrograde monosynaptic tracing indicated extensive integration of transplanted neurons into the surrounding neuronal tracts facilitated by CPTX. Consequently, locomotion and spinal cord conduction significantly improved. Thus, ex vivo gene therapy targeting synapse formation holds promise for future clinical applications and offers potential benefits to individuals with SCI., Competing Interests: Declaration of interests H.O. and M.N. are compensated scientific consultants from K Pharma, and H.O. is also a compensated scientific consultant from San Bio. No management, preparation, analysis, interpretation, or review of data were performed by the funding sources., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
35. Bioorthogonal chemical labeling of endogenous neurotransmitter receptors in living mouse brains.
- Author
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Nonaka H, Sakamoto S, Shiraiwa K, Ishikawa M, Tamura T, Okuno K, Kondo T, Kiyonaka S, Susaki EA, Shimizu C, Ueda HR, Kakegawa W, Arai I, Yuzaki M, and Hamachi I
- Subjects
- Mice, Animals, Indicators and Reagents, Ligands, Brain, Proteins, Neurons
- Abstract
Neurotransmitter receptors are essential components of synapses for communication between neurons in the brain. Because the spatiotemporal expression profiles and dynamics of neurotransmitter receptors involved in many functions are delicately governed in the brain, in vivo research tools with high spatiotemporal resolution for receptors in intact brains are highly desirable. Covalent labeling by chemical reaction (chemical labeling) of proteins without genetic manipulation is now a powerful method for analyzing receptors in vitro. However, selective target receptor labeling in the brain has not yet been achieved. This study shows that ligand-directed alkoxyacylimidazole (LDAI) chemistry can be used to selectively tether synthetic probes to target endogenous receptors in living mouse brains. The reactive LDAI reagents with negative charges were found to diffuse well over the whole brain and could selectively label target endogenous receptors, including AMPAR, NMDAR, mGlu1, and GABA
A R. This simple and robust labeling protocol was then used for various applications: three-dimensional spatial mapping of endogenous receptors in the brains of healthy and disease-model mice; multi-color receptor imaging; and pulse-chase analysis of the receptor dynamics in postnatal mouse brains. Here, results demonstrated that bioorthogonal receptor modification in living animal brains may provide innovative molecular tools that contribute to the in-depth understanding of complicated brain functions., Competing Interests: Competing interests statement:The authors declare no competing interest.- Published
- 2024
- Full Text
- View/download PDF
36. Neuronal DSCAM regulates the peri-synaptic localization of GLAST in Bergmann glia for functional synapse formation.
- Author
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Dewa KI, Arimura N, Kakegawa W, Itoh M, Adachi T, Miyashita S, Inoue YU, Hizawa K, Hori K, Honjoya N, Yagishita H, Taya S, Miyazaki T, Usui C, Tatsumoto S, Tsuzuki A, Uetake H, Sakai K, Yamakawa K, Sasaki T, Nagai J, Kawaguchi Y, Sone M, Inoue T, Go Y, Ichinohe N, Kaibuchi K, Watanabe M, Koizumi S, Yuzaki M, and Hoshino M
- Subjects
- Animals, Mice, Amino Acid Transport System X-AG metabolism, Cerebellum metabolism, Glutamic Acid metabolism, Purkinje Cells metabolism, Synapses metabolism, Neuroglia metabolism, Neurons metabolism
- Abstract
In the central nervous system, astrocytes enable appropriate synapse function through glutamate clearance from the synaptic cleft; however, it remains unclear how astrocytic glutamate transporters function at peri-synaptic contact. Here, we report that Down syndrome cell adhesion molecule (DSCAM) in Purkinje cells controls synapse formation and function in the developing cerebellum. Dscam-mutant mice show defects in CF synapse translocation as is observed in loss of function mutations in the astrocytic glutamate transporter GLAST expressed in Bergmann glia. These mice show impaired glutamate clearance and the delocalization of GLAST away from the cleft of parallel fibre (PF) synapse. GLAST complexes with the extracellular domain of DSCAM. Riluzole, as an activator of GLAST-mediated uptake, rescues the proximal impairment in CF synapse formation in Purkinje cell-selective Dscam-deficient mice. DSCAM is required for motor learning, but not gross motor coordination. In conclusion, the intercellular association of synaptic and astrocyte proteins is important for synapse formation and function in neural transmission., (© 2024. The Author(s).)
- Published
- 2024
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37. Brain-Specific Angiogenesis Inhibitor 3 Is Expressed in the Cochlea and Is Necessary for Hearing Function in Mice.
- Author
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Saegusa C, Kakegawa W, Miura E, Aimi T, Mogi S, Harada T, Yamashita T, Yuzaki M, and Fujioka M
- Subjects
- Animals, Mice, Brain, Hair Cells, Auditory, Outer, Mice, Knockout, Cochlea metabolism, Hearing, Nerve Tissue Proteins genetics, Membrane Proteins genetics
- Abstract
Mammalian auditory hair cells transduce sound-evoked traveling waves in the cochlea into nerve stimuli, which are essential for hearing function. Pillar cells located between the inner and outer hair cells are involved in the formation of the tunnel of Corti, which incorporates outer-hair-cell-driven fluid oscillation and basilar membrane movement, leading to the fine-tuned frequency-specific perception of sounds by the inner hair cells. However, the detailed molecular mechanism underlying the development and maintenance of pillar cells remains to be elucidated. In this study, we examined the expression and function of brain-specific angiogenesis inhibitor 3 (Bai3), an adhesion G-protein-coupled receptor, in the cochlea. We found that Bai3 was expressed in hair cells in neonatal mice and pillar cells in adult mice, and, interestingly, Bai3 knockout mice revealed the abnormal formation of pillar cells, with the elevation of the hearing threshold in a frequency-dependent manner. Furthermore, old Bai3 knockout mice showed the degeneration of hair cells and spiral ganglion neurons in the basal turn. The results suggest that Bai3 plays a crucial role in the development and/or maintenance of pillar cells, which, in turn, are necessary for normal hearing function. Our results may contribute to understanding the mechanisms of hearing loss in human patients.
- Published
- 2023
- Full Text
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38. C1ql1-Bai3 signaling is necessary for climbing fiber synapse formation in mature Purkinje cells in coordination with neuronal activity.
- Author
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Aimi T, Matsuda K, and Yuzaki M
- Subjects
- Animals, Mice, Dendrites, Cerebellum, Brain, Complement C1q, Purkinje Cells, Neurons
- Abstract
Changes in neural activity induced by learning and novel environments have been reported to lead to the formation of new synapses in the adult brain. However, the underlying molecular mechanism is not well understood. Here, we show that Purkinje cells (PCs), which have established adult-type monosynaptic innervation by climbing fibers (CFs) after elimination of weak CFs during development, can be reinnervated by multiple CFs by increased expression of the synaptic organizer C1ql1 in CFs or Bai3, a receptor for C1ql1, in PCs. In the adult cerebellum, CFs are known to have transverse branches that run in a mediolateral direction without forming synapses with PCs. Electrophysiological, Ca
2+ -imaging and immunohistochemical studies showed that overexpression of C1ql1 or Bai3 caused these CF transverse branches to elongate and synapse on the distal dendrites of mature PCs. Mature PCs were also reinnervated by multiple CFs when the glutamate receptor GluD2, which is essential for the maintenance of synapses between granule cells and PCs, was deleted. Interestingly, the effect of GluD2 knockout was not observed in Bai3 knockout PCs. In addition, C1ql1 levels were significantly upregulated in CFs of GluD2 knockout mice, suggesting that endogenous, not overexpressed, C1ql1-Bai3 signaling could regulate the reinnervation of mature PCs by CFs. Furthermore, the effects of C1ql1 and Bai3 overexpression required neuronal activity in the PC and CF, respectively. C1ql1 immunoreactivity at CF-PC synapses was reduced when the neuronal activity of CFs was suppressed. These results suggest that C1ql1-Bai3 signaling may mediate CF synaptogenesis in mature PCs, potentially in concert with neuronal activity., (© 2023. The Author(s).)- Published
- 2023
- Full Text
- View/download PDF
39. Bilateral Axillary Artery Perfusion in Total Arch Replacement.
- Author
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Nishimura Y, Honda K, Yuzaki M, Kunimoto H, Fujimoto T, and Agematsu K
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Retrospective Studies, Postoperative Complications prevention & control, Postoperative Complications epidemiology, Perfusion methods, Blood Vessel Prosthesis Implantation methods, Blood Vessel Prosthesis Implantation adverse effects, Femoral Artery, Cerebral Infarction prevention & control, Cerebral Infarction etiology, Cerebral Infarction epidemiology, Treatment Outcome, Cardiopulmonary Bypass methods, Axillary Artery, Aorta, Thoracic surgery
- Abstract
Background: The site of arterial cannulation is an important consideration in the prevention of cerebral infarction after total arch replacement. We compared the outcomes of cannulation of the bilateral axillary artery, the femoral artery, and central cannulation in total arch replacement., Methods: Enrolled were 242 patients, categorized into three groups according to the arterial cannulation site used: bilateral axillary artery group, 124 patients; femoral artery group, 88 patients; central cannulation group, 30 patients. Selective cerebral perfusion was used for brain protection in all patients. Surgical outcomes, including the incidence of postoperative cerebral infarction, were compared between the groups., Results: Cardiopulmonary bypass time and lower-body circulatory arrest time were significantly shorter in the bilateral axillary artery group. Frozen elephant trunk procedure was performed in 54% of the bilateral axillary artery group (P < .001), and concomitant coronary artery bypass graft surgery was performed in 40% of the central cannulation group (P < .01). Hospital mortality in the bilateral axillary artery group was 1.6%, compared with 1.1% in the femoral artery group, and 0% in the central cannulation group (P = .72). The incidence of permanent neurologic deficit was significantly lower in the bilateral axillary artery group (0.8%) than in the central cannulation group (13%; P = .02). Logistic regression analysis indicated that bilateral axillary artery perfusion was a significant factor in the prevention of permanent neurologic deficit (odds ratio 0.10, P = .03)., Conclusions: Recent technical advances using bilateral axillary artery perfusion and frozen elephant trunk technique were associated with shortening cardiopulmonary bypass time and prevention of postoperative cerebral infarction in total arch replacement., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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40. Rab21 regulates caveolin-1-mediated endocytic trafficking to promote immature neurite pruning.
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Shikanai M, Ito S, Nishimura YV, Akagawa R, Fukuda M, Yuzaki M, Nabeshima YI, and Kawauchi T
- Subjects
- rab5 GTP-Binding Proteins metabolism, Endocytosis, Clathrin metabolism, Caveolin 1 metabolism, Endosomes metabolism
- Abstract
Transmembrane proteins are internalized by clathrin- and caveolin-dependent endocytosis. Both pathways converge on early endosomes and are thought to share the small GTPase Rab5 as common regulator. In contrast to this notion, we show here that the clathrin- and caveolin-mediated endocytic pathways are differentially regulated. Rab5 and Rab21 localize to distinct populations of early endosomes in cortical neurons and preferentially regulate clathrin- and caveolin-mediated pathways, respectively, suggesting heterogeneity in the early endosomes, rather than a converging point. Suppression of Rab21, but not Rab5, results in decreased plasma membrane localization and total protein levels of caveolin-1, which perturbs immature neurite pruning of cortical neurons, an in vivo-specific step of neuronal maturation. Taken together, our data indicate that clathrin- and caveolin-mediated endocytic pathways run in parallel in early endosomes, which show different molecular regulation and physiological function., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)
- Published
- 2023
- Full Text
- View/download PDF
41. Revisiting PFA-mediated tissue fixation chemistry: FixEL enables trapping of small molecules in the brain to visualize their distribution changes.
- Author
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Nonaka H, Mino T, Sakamoto S, Oh JH, Watanabe Y, Ishikawa M, Tsushima A, Amaike K, Kiyonaka S, Tamura T, Aricescu AR, Kakegawa W, Miura E, Yuzaki M, and Hamachi I
- Abstract
Various small molecules have been used as functional probes for tissue imaging in medical diagnosis and pharmaceutical drugs for disease treatment. The spatial distribution, target selectivity, and diffusion/excretion kinetics of small molecules in structurally complicated specimens are critical for function. However, robust methods for precisely evaluating these parameters in the brain have been limited. Herein, we report a new method termed "fixation-driven chemical cross-linking of exogenous ligands ( FixEL )," which traps and images exogenously administered molecules of interest (MOIs) in complex tissues. This method relies on protein-MOI interactions and chemical cross-linking of amine-tethered MOI with paraformaldehyde used for perfusion fixation. FixEL is used to obtain images of the distribution of the small molecules, which addresses selective/nonselective binding to proteins, time-dependent localization changes, and diffusion/retention kinetics of MOIs such as the scaffold of PET tracer derivatives or drug-like small molecules., Competing Interests: Declaration of Interests The authors (K.A., S.K., and I.H.) have filed a patent application (WO2019/168125).
- Published
- 2023
- Full Text
- View/download PDF
42. In vivo nanoscopic landscape of neurexin ligands underlying anterograde synapse specification.
- Author
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Nozawa K, Sogabe T, Hayashi A, Motohashi J, Miura E, Arai I, and Yuzaki M
- Subjects
- Animals, Cell Adhesion Molecules, Neuronal genetics, Cell Adhesion Molecules, Neuronal metabolism, Epitopes, Glutamic Acid, Ligands, Membrane Proteins genetics, Membrane Proteins metabolism, Mice, N-Methylaspartate, Receptors, Glutamate genetics, Receptors, Glutamate metabolism, Receptors, Presynaptic, Synapses physiology, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Receptors, AMPA
- Abstract
Excitatory synapses are formed and matured by the cooperative actions of synaptic organizers, such as neurexins (Nrxns), neuroligins (Nlgns), LRRTMs, and Cbln1. Recent super-resolution nanoscopy developments have revealed that many synaptic organizers, as well as glutamate receptors and glutamate release machinery, exist as nanoclusters within synapses. However, it is unclear how such nanodomains interact with each other to organize excitatory synapses in vivo. By applying X10 expansion microscopy to epitope tag knockin mice, we found that Cbln1, Nlgn1, and LRRTM1, which share Nrxn as a common presynaptic receptor, form overlapping or separate nanodomains depending on Nrxn with or without a sequence encoded by splice site 4. The size and position of glutamate receptor nanodomains of GluD1, NMDA, and AMPA receptors were regulated by Cbln1, Nlgn1, and LRRTM1 nanodomains, respectively. These findings indicate that Nrxns anterogradely regulate the postsynaptic nanoscopic architecture of glutamate receptors through competition and coordination of Nrxn ligands., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
43. The complement C3-complement factor D-C3a receptor signalling axis regulates cardiac remodelling in right ventricular failure.
- Author
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Ito S, Hashimoto H, Yamakawa H, Kusumoto D, Akiba Y, Nakamura T, Momoi M, Komuro J, Katsuki T, Kimura M, Kishino Y, Kashimura S, Kunitomi A, Lachmann M, Shimojima M, Yozu G, Motoda C, Seki T, Yamamoto T, Shinya Y, Hiraide T, Kataoka M, Kawakami T, Suzuki K, Ito K, Yada H, Abe M, Osaka M, Tsuru H, Yoshida M, Sakimura K, Fukumoto Y, Yuzaki M, Fukuda K, and Yuasa S
- Subjects
- Animals, Complement C3 genetics, Complement C3-C5 Convertases, Complement Factor D, Mice, Mice, Knockout, Ventricular Remodeling, Heart Failure genetics, Ventricular Dysfunction, Right
- Abstract
Failure of the right ventricle plays a critical role in any type of heart failure. However, the mechanism remains unclear, and there is no specific therapy. Here, we show that the right ventricle predominantly expresses alternative complement pathway-related genes, including Cfd and C3aR1. Complement 3 (C3)-knockout attenuates right ventricular dysfunction and fibrosis in a mouse model of right ventricular failure. C3a is produced from C3 by the C3 convertase complex, which includes the essential component complement factor D (Cfd). Cfd-knockout mice also show attenuation of right ventricular failure. Moreover, the plasma concentration of CFD correlates with the severity of right ventricular failure in patients with chronic right ventricular failure. A C3a receptor (C3aR) antagonist dramatically improves right ventricular dysfunction in mice. In summary, we demonstrate the crucial role of the C3-Cfd-C3aR axis in right ventricular failure and highlight potential therapeutic targets for right ventricular failure., (© 2022. The Author(s).)
- Published
- 2022
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- View/download PDF
44. Coordination chemogenetics for activation of GPCR-type glutamate receptors in brain tissue.
- Author
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Ojima K, Kakegawa W, Yamasaki T, Miura Y, Itoh M, Michibata Y, Kubota R, Doura T, Miura E, Nonaka H, Mizuno S, Takahashi S, Yuzaki M, Hamachi I, and Kiyonaka S
- Subjects
- Animals, Brain, Mice, Neuronal Plasticity, Cerebellum, Palladium
- Abstract
Direct activation of cell-surface receptors is highly desirable for elucidating their physiological roles. A potential approach for cell-type-specific activation of a receptor subtype is chemogenetics, in which both point mutagenesis of the receptors and designed ligands are used. However, ligand-binding properties are affected in most cases. Here, we developed a chemogenetic method for direct activation of metabotropic glutamate receptor 1 (mGlu1), which plays essential roles in cerebellar functions in the brain. Our screening identified a mGlu1 mutant, mGlu1(N264H), that was activated directly by palladium complexes. A palladium complex showing low cytotoxicity successfully activated mGlu1 in mGlu1(N264H) knock-in mice, revealing that activation of endogenous mGlu1 is sufficient to evoke the critical cellular mechanism of synaptic plasticity, a basis of motor learning in the cerebellum. Moreover, cell-type-specific activation of mGlu1 was demonstrated successfully using adeno-associated viruses in mice, which shows the potential utility of this chemogenetics for clarifying the physiological roles of mGlu1 in a cell-type-specific manner., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
45. Subunit-dependent and subunit-independent rules of AMPA receptor trafficking during chemical long-term depression in hippocampal neurons.
- Author
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Matsuda S and Yuzaki M
- Subjects
- Animals, Rats, Endosomes metabolism, Adaptor Protein Complex 2 metabolism, Adaptor Protein Complex 3 metabolism, Adaptor Protein Complex 3 genetics, Phosphorylation, Protein Subunits metabolism, Humans, Receptors, AMPA metabolism, Hippocampus metabolism, Hippocampus cytology, Neurons metabolism, Protein Transport, Long-Term Synaptic Depression physiology
- Abstract
Long-term potentiation (LTP) and long-term depression (LTD) of excitatory neurotransmission are believed to be the neuronal basis of learning and memory. Both processes are primarily mediated by neuronal activity-induced transport of postsynaptic AMPA-type glutamate receptors (AMPARs). While AMPAR subunits and their specific phosphorylation sites mediate differential AMPAR trafficking, LTP and LTD could also occur in a subunit-independent manner. Thus, it remains unclear whether and how certain AMPAR subunits with phosphorylation sites are preferentially recruited to or removed from synapses during LTP and LTD. Using immunoblot and immunocytochemical analysis, we show that phosphomimetic mutations of the membrane-proximal region (MPR) in GluA1 AMPAR subunits affect the subunit-dependent endosomal transport of AMPARs during chemical LTD. AP-2 and AP-3, adaptor protein complexes necessary for clathrin-mediated endocytosis and late endosomal/lysosomal trafficking, respectively, are reported to be recruited to AMPARs by binding to the AMPAR auxiliary subunit, stargazin (STG), in an AMPAR subunit-independent manner. However, the association of AP-3, but not AP-2, with STG was indirectly inhibited by the phosphomimetic mutation in the MPR of GluA1. Thus, although AMPARs containing the phosphomimetic mutation at the MPR of GluA1 were endocytosed by a chemical LTD-inducing stimulus, they were quickly recycled back to the cell surface in hippocampal neurons. These results could explain how the phosphorylation status of GluA1-MPR plays a dominant role in subunit-independent STG-mediated AMPAR trafficking during LTD., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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- View/download PDF
46. "Scrap & build" functional circuits: Molecular and cellular basis of neural remodeling.
- Author
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Emoto K, Hensch TK, and Yuzaki M
- Published
- 2021
- Full Text
- View/download PDF
47. Destroy the old to build the new: Activity-dependent lysosomal exocytosis in neurons.
- Author
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Ibata K and Yuzaki M
- Subjects
- Exocytosis, Humans, Lysosomes, Neurons, Receptors, AMPA, Neurodegenerative Diseases
- Abstract
Lysosomes are organelles that support diverse cellular functions such as terminal degradation of macromolecules and nutrient recycling. Additionally, lysosomes can fuse with the plasma membrane, a phenomenon referred to as lysosomal exocytosis, to release their contents, including hydrolytic enzymes and cargo proteins. Recently, neuronal activity has been shown to induce lysosomal exocytosis in dendrites and axons. Secreted lysosomal enzyme cathepsin B induces and stabilizes synaptic structural changes by degrading the local extracellular matrix. Extracellular matrix reorganization could also enhance the lateral diffusion of the co-released synaptic organizer Cbln1 along the surface of axons to facilitate new synapse formation. Similarly, lateral diffusion of dendritic AMPA-type glutamate receptors could be facilitated to enhance functional synaptic plasticity. Therefore, lysosomal exocytosis is a powerful way of building new cellular structures through the coordinated destruction of the old environment. Understanding the mechanisms by which lysosomal exocytosis is regulated in neurons is expected to lead to the development of new therapeutics for neuronal plasticity following spinal cord injury or neurodegenerative disease., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
48. Masao Ito-A Visionary Neuroscientist with a Passion for the Cerebellum.
- Author
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Nagao S, Hirai H, Kano M, and Yuzaki M
- Subjects
- Emotions, Cerebellum, Neurosciences
- Published
- 2021
- Full Text
- View/download PDF
49. Serum Cystatin C Level as a Biomarker of Aortic Plaque in Patients with an Aortic Arch Aneurysm.
- Author
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Nishimura Y, Honda K, Yuzaki M, Tajima K, Nakamura R, Nakanishi Y, Kaneko M, Agematsu K, and Nagashima M
- Subjects
- Aged, Aged, 80 and over, Aortic Aneurysm, Thoracic surgery, Biomarkers blood, Creatinine blood, Female, Humans, Male, Plaque, Atherosclerotic complications, Renal Insufficiency, Chronic blood, Renal Insufficiency, Chronic complications, Retrospective Studies, Aortic Aneurysm, Thoracic blood, Aortic Aneurysm, Thoracic complications, Cystatin C blood, Plaque, Atherosclerotic blood, Plaque, Atherosclerotic diagnosis
- Abstract
Aim: During surgery for an aortic arch aneurysm, aortic plaque in the descending aorta should be evaluated, but there are currently no suitable biomarkers for it. Surgeons should be especially aware of cerebral embolism from femoral perfusion and of peripheral embolism from stent graft deployment. Cystatin C is a known useful marker of renal dysfunction with a role as a biomarker for severity of coronary artery disease. In the absence of a suitable biomarker for aortic plaque in the descending aorta, we examine cystatin C as a candidate., Methods: In all, 75 patients who underwent surgery for an aortic arch aneurysm were enrolled. They were divided into two groups, depending on whether they had chronic kidney disease or not. The serum cystatin C value and creatinine value were evaluated preoperatively. The aortic plaque volume ratio and components in the descending aorta were calculated from preoperative enhanced computed tomography., Results: The soft plaque volume ratio was higher in patients with chronic kidney disease than in patients without it. Cystatin C positively correlated with the total aortic plaque volume ratio in all cases, and it positively correlated with the soft plaque volume ratio in both groups. Creatinine had no correlation with any type of plaque volume ratio in either group. In patients without chronic kidney disease, the soft plaque volume ratio was higher in patients with higher cystatin C levels than in patients with normal levels., Conclusion: The preoperative serum cystatin C level could be a biomarker of aortic plaque in the descending aorta in patients with an aortic arch aneurysm.
- Published
- 2021
- Full Text
- View/download PDF
50. The autism-associated protein CHD8 is required for cerebellar development and motor function.
- Author
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Kawamura A, Katayama Y, Kakegawa W, Ino D, Nishiyama M, Yuzaki M, and Nakayama KI
- Subjects
- Animals, Behavior, Animal, Cell Differentiation, Cell Line, Cell Proliferation, Cerebellum abnormalities, Chromatin metabolism, DNA-Binding Proteins deficiency, Developmental Disabilities, Gene Deletion, Gene Expression Regulation, Developmental, Male, Mice, Inbred C57BL, Nervous System Malformations, Neural Stem Cells metabolism, Neurons metabolism, Synapses metabolism, Mice, Autistic Disorder pathology, Cerebellum embryology, Cerebellum physiopathology, DNA-Binding Proteins metabolism, Motor Activity
- Abstract
Mutations in the gene encoding the chromatin remodeler chromodomain helicase DNA-binding protein 8 (CHD8) are a highly penetrant risk factor for autism spectrum disorder (ASD). Although cerebellar abnormalities have long been thought to be related to ASD pathogenesis, it has remained largely unknown whether dysfunction of CHD8 in the cerebellum contributes to ASD phenotypes. We here show that cerebellar granule neuron progenitor (GNP)-specific deletion of Chd8 in mice impairs the proliferation and differentiation of these cells as well as gives rise to cerebellar hypoplasia and a motor coordination defect, but not to ASD-like behavioral abnormalities. CHD8 is found to regulate the expression of neuronal genes in GNPs. It also binds preferentially to promoter regions and modulates local chromatin accessibility of transcriptionally active genes in these cells. Our results have thus uncovered a key role for CHD8 in cerebellar development, with important implications for understanding the contribution of this brain region to ASD pathogenesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
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