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1,251 results on '"WANG, Hong-Gang"'

1. Drp1 splice variants regulate ovarian cancer mitochondrial dynamics and tumor progression

Author

Javed, Zaineb, Shin, Dong Hui, Pan, Weihua, White, Sierra R, Elhaw, Amal Taher, Kim, Yeon Soo, Kamlapurkar, Shriya, Cheng, Ya-Yun, Benson, J Cory, Abdelnaby, Ahmed Emam, Phaëton, Rébécca, Wang, Hong-Gang, Yang, Shengyu, Sullivan, Mara L G, St.Croix, Claudette M, Watkins, Simon C, Mullett, Steven J, Gelhaus, Stacy L, Lee, Nam, Coffman, Lan G, Aird, Katherine M, Trebak, Mohamed, Mythreye, Karthikeyan, Walter, Vonn, and Hempel, Nadine

Published
2024
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3. Multiple beta cell-independent mechanisms drive hypoglycemia in Timothy syndrome

Author

Matsui, Maiko, Lynch, Lauren E., Distefano, Isabella, Galante, Allison, Gade, Aravind R., Wang, Hong-Gang, Gómez-Banoy, Nicolas, Towers, Patrick, Sinden, Daniel S., Wei, Eric Q., Barnett, Adam S., Johnson, Kenneth, Lima, Renan, Rubio-Navarro, Alfonso, Li, Ang K., Marx, Steven O., McGraw, Timothy E., Thornton, Paul S., Timothy, Katherine W., Lo, James C., and Pitt, Geoffrey S.

Published
2024
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12. A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission

Author

Flower, Thomas G, Takahashi, Yoshinori, Hudait, Arpa, Rose, Kevin, Tjahjono, Nicholas, Pak, Alexander J, Yokom, Adam L, Liang, Xinwen, Wang, Hong-Gang, Bouamr, Fadila, Voth, Gregory A, and Hurley, James H

Subjects
Biochemistry and Cell Biology, Chemical Sciences, Biological Sciences, HIV/AIDS, Infectious Diseases, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Adaptor Proteins, Signal Transducing, Amino Acid Motifs, Autophagosomes, Cell Membrane, Crystallization, Crystallography, X-Ray, DNA-Binding Proteins, Endosomal Sorting Complexes Required for Transport, HEK293 Cells, HIV-1, Host-Pathogen Interactions, Humans, Molecular Dynamics Simulation, Phosphoproteins, Protein Conformation, Transcription Factors, Virus Release, gag Gene Products, Human Immunodeficiency Virus, Medical and Health Sciences, Biophysics, Developmental Biology, Biological sciences, Biomedical and clinical sciences, Chemical sciences
Abstract

The ESCRT complexes drive membrane scission in HIV-1 release, autophagosome closure, multivesicular body biogenesis, cytokinesis, and other cell processes. ESCRT-I is the most upstream complex and bridges the system to HIV-1 Gag in virus release. The crystal structure of the headpiece of human ESCRT-I comprising TSG101-VPS28-VPS37B-MVB12A was determined, revealing an ESCRT-I helical assembly with a 12-molecule repeat. Electron microscopy confirmed that ESCRT-I subcomplexes form helical filaments in solution. Mutation of VPS28 helical interface residues blocks filament formation in vitro and autophagosome closure and HIV-1 release in human cells. Coarse-grained (CG) simulations of ESCRT assembly at HIV-1 budding sites suggest that formation of a 12-membered ring of ESCRT-I molecules is a geometry-dependent checkpoint during late stages of Gag assembly and HIV-1 budding and templates ESCRT-III assembly for membrane scission. These data show that ESCRT-I is not merely a bridging adaptor; it has an essential scaffolding and mechanical role in its own right.

Published
2020

20. Multi Mode Interactive Information Processing Method in Online Education System of Ideological and Political Course

Author

Wang, Hong-gang, Xu, Li-tang, Akan, Ozgur, Editorial Board Member, Bellavista, Paolo, Editorial Board Member, Cao, Jiannong, Editorial Board Member, Coulson, Geoffrey, Editorial Board Member, Dressler, Falko, Editorial Board Member, Ferrari, Domenico, Editorial Board Member, Gerla, Mario, Editorial Board Member, Kobayashi, Hisashi, Editorial Board Member, Palazzo, Sergio, Editorial Board Member, Sahni, Sartaj, Editorial Board Member, Shen, Xuemin (Sherman), Editorial Board Member, Stan, Mircea, Editorial Board Member, Jia, Xiaohua, Editorial Board Member, Zomaya, Albert Y., Editorial Board Member, Fu, Weina, editor, Liu, Shuai, editor, and Dai, Jianhua, editor

Published
2021
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21. Design of Personal Learning Model Recognition Model for Online Teaching of Ideological and Political Theory Course

Author

Xu, Li-tang, Wang, Hong-gang, Akan, Ozgur, Editorial Board Member, Bellavista, Paolo, Editorial Board Member, Cao, Jiannong, Editorial Board Member, Coulson, Geoffrey, Editorial Board Member, Dressler, Falko, Editorial Board Member, Ferrari, Domenico, Editorial Board Member, Gerla, Mario, Editorial Board Member, Kobayashi, Hisashi, Editorial Board Member, Palazzo, Sergio, Editorial Board Member, Sahni, Sartaj, Editorial Board Member, Shen, Xuemin (Sherman), Editorial Board Member, Stan, Mircea, Editorial Board Member, Jia, Xiaohua, Editorial Board Member, Zomaya, Albert Y., Editorial Board Member, Fu, Weina, editor, Liu, Shuai, editor, and Dai, Jianhua, editor

Published
2021
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23. Research on the Optimization of the Allocation of Educational Resources in Modern History Based on Demand Features

Author

Wang, Hong-Gang, Xia, Jing, Akan, Ozgur, Editorial Board Member, Bellavista, Paolo, Editorial Board Member, Cao, Jiannong, Editorial Board Member, Coulson, Geoffrey, Editorial Board Member, Dressler, Falko, Editorial Board Member, Ferrari, Domenico, Editorial Board Member, Gerla, Mario, Editorial Board Member, Kobayashi, Hisashi, Editorial Board Member, Palazzo, Sergio, Editorial Board Member, Sahni, Sartaj, Editorial Board Member, Shen, Xuemin (Sherman), Editorial Board Member, Stan, Mircea, Editorial Board Member, Jia, Xiaohua, Editorial Board Member, Zomaya, Albert Y., Editorial Board Member, Liu, Shuai, editor, Sun, Guanglu, editor, and Fu, Weina, editor

Published
2020
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24. Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations

Author

Rodan, Lance H., Spillmann, Rebecca C., Kurata, Harley T., Lamothe, Shawn M., Maghera, Jasmine, Jamra, Rami Abou, Alkelai, Anna, Antonarakis, Stylianos E., Atallah, Isis, Bar-Yosef, Omer, Bilan, Frédéric, Bjorgo, Kathrine, Blanc, Xavier, Van Bogaert, Patrick, Bolkier, Yoav, Burrage, Lindsay C., Christ, Björn U., Granadillo, Jorge L., Dickson, Patricia, Donald, Kirsten A., Dubourg, Christèle, Eliyahu, Aviva, Emrick, Lisa, Engleman, Kendra, Gonfiantini, Michaela Veronika, Good, Jean-Marc, Kalser, Judith, Kloeckner, Chiara, Lachmeijer, Guus, Macchiaiolo, Marina, Nicita, Francesco, Odent, Sylvie, O’Heir, Emily, Ortiz-Gonzalez, Xilma, Pacio-Miguez, Marta, Palomares-Bralo, María, Pena, Loren, Platzer, Konrad, Quinodoz, Mathieu, Ranza, Emmanuelle, Rosenfeld, Jill A., Roulet-Perez, Eliane, Santani, Avni, Santos-Simarro, Fernando, Pode-Shakked, Ben, Skraban, Cara, Slaugh, Rachel, Superti-Furga, Andrea, Thiffault, Isabelle, van Jaabrsveld, Richard H., Vincent, Marie, Wang, Hong-Gang, Zacher, Pia, Alejandro, Mercedes E., Azamian, Mahshid S., Bacino, Carlos A., Balasubramanyam, Ashok, Chao, Hsiao-Tuan, Clark, Gary D., Craigen, William J., Dai, Hongzheng, Dhar, Shweta U., Emrick, Lisa T., Goldman, Alica M., Hanchard, Neil A., Jamal, Fariha, Karaviti, Lefkothea, Lalani, Seema R., Lee, Brendan H., Lewis, Richard A., Marom, Ronit, Moretti, Paolo M., Murdock, David R., Nicholas, Sarah K., Orengo, James P., Posey, Jennifer E., Potocki, Lorraine, Samson, Susan L., Scott, Daryl A., Tran, Alyssa A., Vogel, Tiphanie P., Wangler, Michael F., Yamamoto, Shinya, Eng, Christine M., Liu, Pengfei, Ward, Patricia A., Behrens, Edward, Deardorff, Matthew, Falk, Marni, Hassey, Kelly, Sullivan, Kathleen, Vanderver, Adeline, Goldstein, David B., Cope, Heidi, McConkie-Rosell, Allyn, Schoch, Kelly, Shashi, Vandana, Smith, Edward C., Sullivan, Jennifer A., Tan, Queenie K.-G., Walley, Nicole M., Agrawal, Pankaj B., Beggs, Alan H., Berry, Gerard T., Briere, Lauren C., Cobban, Laurel A., Coggins, Matthew, Cooper, Cynthia M., Fieg, Elizabeth L., High, Frances, Holm, Ingrid A., Korrick, Susan, Krier, Joel B., Lincoln, Sharyn A., Loscalzo, Joseph, Maas, Richard L., MacRae, Calum A., Pallais, J. Carl, Rao, Deepak A., Silverman, Edwin K., Stoler, Joan M., Sweetser, David A., Walker, Melissa, Walsh, Chris A., Esteves, Cecilia, Kelley, Emily G., Kohane, Isaac S., LeBlanc, Kimberly, McCray, Alexa T., Nagy, Anna, Dasari, Surendra, Lanpher, Brendan C., Lanza, Ian R., Morava, Eva, Oglesbee, Devin, Bademci, Guney, Barbouth, Deborah, Bivona, Stephanie, Carrasquillo, Olveen, Chang, Ta Chen Peter, Forghani, Irman, Grajewski, Alana, Isasi, Rosario, Lam, Byron, Levitt, Roy, Liu, Xue Zhong, McCauley, Jacob, Sacco, Ralph, Saporta, Mario, Schaechter, Judy, Tekin, Mustafa, Telischi, Fred, Thorson, Willa, Zuchner, Stephan, Colley, Heather A., Dayal, Jyoti G., Eckstein, David J., Findley, Laurie C., Krasnewich, Donna M., Mamounas, Laura A., Manolio, Teri A., Mulvihill, John J., LaMoure, Grace L., Goldrich, Madison P., Urv, Tiina K., Doss, Argenia L., Acosta, Maria T., Bonnenmann, Carsten, D’Souza, Precilla, Draper, David D., Ferreira, Carlos, Godfrey, Rena A., Groden, Catherine A., Macnamara, Ellen F., Maduro, Valerie V., Markello, Thomas C., Nath, Avi, Novacic, Donna, Pusey, Barbara N., Toro, Camilo, Wahl, Colleen E., Baker, Eva, Burke, Elizabeth A., Adams, David R., Gahl, William A., Malicdan, May Christine V., Tifft, Cynthia J., Wolfe, Lynne A., Yang, John, Power, Bradley, Gochuico, Bernadette, Huryn, Laryssa, Latham, Lea, Davis, Joie, Mosbrook-Davis, Deborah, Rossignol, Francis, Ben Solomon, MacDowall, John, Thurm, Audrey, Zein, Wadih, Yousef, Muhammad, Adam, Margaret, Amendola, Laura, Bamshad, Michael, Beck, Anita, Bennett, Jimmy, Berg-Rood, Beverly, Blue, Elizabeth, Boyd, Brenna, Byers, Peter, Chanprasert, Sirisak, Cunningham, Michael, Dipple, Katrina, Doherty, Daniel, Earl, Dawn, Glass, Ian, Golden-Grant, Katie, Hahn, Sihoun, Hing, Anne, Hisama, Fuki M., Horike-Pyne, Martha, Jarvik, Gail P., Jarvik, Jeffrey, Jayadev, Suman, Lam, Christina, Maravilla, Kenneth, Mefford, Heather, Merritt, J. Lawrence, Mirzaa, Ghayda, Nickerson, Deborah, Raskind, Wendy, Rosenwasser, Natalie, Scott, C. Ron, Sun, Angela, Sybert, Virginia, Wallace, Stephanie, Wener, Mark, Wenger, Tara, Ashley, Euan A., Bejerano, Gill, Bernstein, Jonathan A., Bonner, Devon, Coakley, Terra R., Fernandez, Liliana, Fisher, Paul G., Fresard, Laure, Hom, Jason, Huang, Yong, Kohler, Jennefer N., Kravets, Elijah, Majcherska, Marta M., Martin, Beth A., Marwaha, Shruti, McCormack, Colleen E., Raja, Archana N., Reuter, Chloe M., Ruzhnikov, Maura, Sampson, Jacinda B., Smith, Kevin S., Sutton, Shirley, Tabor, Holly K., Tucker, Brianna M., Wheeler, Matthew T., Zastrow, Diane B., Zhao, Chunli, Byrd, William E., Crouse, Andrew B., Might, Matthew, Nakano-Okuno, Mariko, Whitlock, Jordan, Brown, Gabrielle, Butte, Manish J., Dell’Angelica, Esteban C., Dorrani, Naghmeh, Douine, Emilie D., Fogel, Brent L., Gutierrez, Irma, Huang, Alden, Krakow, Deborah, Lee, Hane, Loo, Sandra K., Mak, Bryan C., Martin, Martin G., Martínez-Agosto, Julian A., McGee, Elisabeth, Nelson, Stanley F., Nieves-Rodriguez, Shirley, Palmer, Christina G.S., Papp, Jeanette C., Parker, Neil H., Renteria, Genecee, Signer, Rebecca H., Sinsheimer, Janet S., Wan, Jijun, Wang, Lee-kai, Perry, Katherine Wesseling, Woods, Jeremy D., Alvey, Justin, Andrews, Ashley, Bale, Jim, Bohnsack, John, Botto, Lorenzo, Carey, John, Pace, Laura, Longo, Nicola, Marth, Gabor, Moretti, Paolo, Quinlan, Aaron, Velinder, Matt, Viskochil, Dave, Bayrak-Toydemir, Pinar, Mao, Rong, Westerfield, Monte, Bican, Anna, Brokamp, Elly, Duncan, Laura, Hamid, Rizwan, Kennedy, Jennifer, Kozuira, Mary, Newman, John H., PhillipsIII, John A., Rives, Lynette, Robertson, Amy K., Solem, Emily, Cogan, Joy D., Cole, F. Sessions, Hayes, Nichole, Kiley, Dana, Sisco, Kathy, Wambach, Jennifer, Wegner, Daniel, Baldridge, Dustin, Pak, Stephen, Schedl, Timothy, Shin, Jimann, Solnica-Krezel, Lilianna, Rush, Eric, Pitt, Geoffrey S., and Au, Ping Yee Billie

Published
2021
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27. The Worries of Out‐of‐Home Activities in Patients With Inflammatory Bowel Disease: A Survey Study During the COVID‐19 Pandemic.

Author

Fei, Yun-Hui, Zhang, Meng-Hui, Zhang, Min-Na, Shen, Zhao, Wang, Hong-Gang, and Day, Andrew S.

Subjects
CROSS-sectional method, RESTROOMS, WORRY, ACADEMIC medical centers, OUTPATIENT services in hospitals, RESEARCH funding, CROHN'S disease, TRAVEL, QUESTIONNAIRES, SEX distribution, AGE distribution, ULCERATIVE colitis, DESCRIPTIVE statistics, INFLAMMATORY bowel diseases, SURVEYS, QUALITY of life, DEFECATION, COVID-19 pandemic, SOCIAL participation
Abstract

Background: Patients with inflammatory bowel disease (IBD) often experience worries related to travel due to frequent bowel movements. However, there is currently limited research focusing on the travel worries of patients with IBD. The aim of this study was to assess the level of worry regarding out‐of‐home activities in patients with IBD and identify factors associated with worry. Methods: This study included patients with IBD who visited the outpatient clinics between September 2020 and March 2022, during the COVID‐19 pandemic. Participants completed a self‐designed questionnaire, providing general clinical data and indicating their level of worry for out‐of‐home activities. Results: A total of 529 patients with IBD completed the questionnaire. Patients with Crohn's disease (CD) had a higher proportion of individuals under 40 years old and males compared to patients with ulcerative colitis (UC). Regarding out‐of‐home activities, patients with UC expressed greater worry about going out and taking buses than patients with CD. However, there were no significant differences observed between the two groups in terms of travel worries and worries about finding public washrooms. A significant majority (85.4%) of patients with clinically active IBD expressed worries about not finding public washrooms when going out, while 46.7% of patients in clinical remission had similar worries. Moreover, the worry about finding public washrooms was higher in patients with UC compared to those with CD, both during the clinical activity and remission. Conclusion: This survey conducted during the COVID‐19 pandemic reported worries among patients with IBD about out‐of‐home activities. The patients with clinically active IBD, especially UC, expressed worries about not finding public washrooms when going out. We highlight the actual psychological and quality of life challenges faced by patients with IBD. [ABSTRACT FROM AUTHOR]

Published
2024
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35. Sphingolipid metabolism determines the therapeutic efficacy of nanoliposomal ceramide in acute myeloid leukemia

Author

Barth, Brian M., Wang, Weiyuan, Toran, Paul T., Fox, Todd E., Annageldiyev, Charyguly, Ondrasik, Regina M., Keasey, Nicole R., Brown, Timothy J., Devine, Viola G., Sullivan, Emily C., Cote, Andrea L., Papakotsi, Vasiliki, Tan, Su-Fern, Shanmugavelandy, Sriram S., Deering, Tye G., Needle, David B., Stern, Stephan T., Zhu, Junjia, Liao, Jason, Viny, Aaron D., Feith, David J., Levine, Ross L., Wang, Hong-Gang, Loughran, Thomas P., Jr, Sharma, Arati, Kester, Mark, and Claxton, David F.

Published
2019
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37. Genetic, Cellular, and Functional Evidence for Ca2+ Inflow through Cav1.2 and Cav1.3 Channels in Murine Spiral Ganglion Neurons

Author

Lv, Ping, Kim, Hyo Jeong, Lee, Jeong-Han, Sihn, Choong-Ryoul, Gharaie, Somayeh Fathabad, Mousavi-Nik, Atefeh, Wang, Wenying, Wang, Hong-Gang, Gratton, Michael Anne, Doyle, Karen J, Zhang, Xiao-Dong, Chiamvimonvat, Nipavan, and Yamoah, Ebenezer N

Subjects
Biomedical and Clinical Sciences, Medical Physiology, Neurosciences, Genetics, 1.1 Normal biological development and functioning, Underpinning research, Neurological, Action Potentials, Animals, Calcium, Calcium Channels, L-Type, Cochlea, Female, Gene Expression Regulation, HEK293 Cells, Humans, In Vitro Techniques, Male, Membrane Transport Modulators, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Spiral Ganglion, Tubulin, action potentials, calcium channels, deafness, hearing, neuronal degeneration, neuronal survival, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

Spiral ganglion neurons (SGNs) of the eighth nerve serve as the bridge between hair cells and the cochlear nucleus. Hair cells use Cav1.3 as the primary channel for Ca(2+) inflow to mediate transmitter release. In contrast, SGNs are equipped with multiple Ca(2+) channels to mediate Ca(2+)-dependent functions. We examined directly the role of Cav1.3 channels in SGNs using Cav1.3-deficient mice (Cav1.3(-/-)). We revealed a surprising finding that SGNs functionally express the cardiac-specific Cav1.2, as well as neuronal Cav1.3 channels. We show that evoked action potentials recorded from SGNs show a significant decrease in the frequency of firing in Cav1.3(-/-) mice compared with wild-type (Cav1.3(+/+)) littermates. Although Cav1.3 is the designated L-type channel in neurons, whole-cell currents recorded in isolated SGNs from Cav1.3(-/-) mice showed a surprising remnant current with sensitivity toward the dihydropyridine (DHP) agonist and antagonist, and a depolarization shift in the voltage-dependent activation compared with that in the Cav1.3(+/+) mice. Indeed, direct measurement of the elementary properties of Ca(2+) channels, in Cav1.3(+/+) neurons, confirmed the existence of two DHP-sensitive single-channel currents, with distinct open probabilities and conductances. We demonstrate that the DHP-sensitive current in Cav1.3(-/-) mice is derived from Cav1.2 channel activity, providing for the first time, to our knowledge, functional data for the expression of Cav1.2 currents in neurons. Finally, using shRNA gene knockdown methodology, and histological analyses of SGNs from Cav1.2(+/-) and Cav1.3(+/-) mice, we were able to establish the differential roles of Cav1.2 and Cav1.3 in SGNs.

Published
2014

38. Iron inhibits glioblastoma cell migration and polarization

Author

Shenoy, Ganesh, primary, Kheirabadi, Sina, additional, Ataie, Zaman, additional, Sahu, Aurosman Pappus, additional, Palsa, Kondaiah, additional, Wade, Quinn, additional, Khunsriraksakul, Chachrit, additional, Khristov, Vladimir, additional, Slagle‐Webb, Becky, additional, Lathia, Justin D., additional, Wang, Hong‐Gang, additional, Sheikhi, Amir, additional, and Connor, James R., additional

Published
2023
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41. Acid Ceramidase Inhibitor LCL-805 Antagonizes Akt Signaling and Promotes Iron-Dependent Cell Death in Acute Myeloid Leukemia

Author

Ung, Johnson, primary, Tan, Su-Fern, additional, Fox, Todd E, additional, Shaw, Jeremy JP, additional, Taori, Maansi, additional, Horton, Bethany J, additional, Golla, Upendarrao, additional, Sharma, Arati, additional, Szulc, Zdzislaw M, additional, Wang, Hong-Gang, additional, Chalfant, Charles E., additional, Cabot, Myles C, additional, Claxton, David F, additional, Loughran, Thomas P, additional, and Feith, David J, additional

Published
2023
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43. Extracellular vesicles from retinal pigment epithelial cells expressing R345W‐Fibulin‐3 induce epithelial‐mesenchymal transition in recipient cells

Author

Zhou, Mi, primary, Zhao, Yuanjun, additional, Weber, Sarah R., additional, Gates, Christopher, additional, Carruthers, Nicholas J., additional, Chen, Han, additional, Liu, Xiaoming, additional, Wang, Hong‐Gang, additional, Ford, Michael, additional, Swulius, Matthew T., additional, Barber, Alistair J., additional, Grillo, Stephanie L., additional, and Sundstrom, Jeffrey M., additional

Published
2023
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44. Alternate splice variants of the mitochondrial fission proteinDNM1L/Drp1 regulate mitochondrial dynamics and cell fate in ovarian cancer

Author

Javed, Zaineb, primary, Shin, Dong Hui, additional, Pan, Weihua, additional, White, Sierra R., additional, Kim, Yeon Soo, additional, Elhaw, Amal Taher, additional, Kamlapurkar, Shriya, additional, Cheng, Ya-Yun, additional, Benson, J Cory, additional, Abdelnaby, Ahmed Emam, additional, Phaeton, Rebecca, additional, Wang, Hong-Gang, additional, Yang, Shengyu, additional, Sullivan, Mara L.G., additional, Watkins, Simon C., additional, Mullett, Steven J., additional, Gelhaus, Stacy L., additional, Lee, Nam, additional, Coffman, Lan G., additional, Aird, Katherine M., additional, Trebak, Mohamed, additional, Mythreye, Karthikeyan, additional, Walter, Vonn, additional, and Hempel, Nadine, additional

Published
2023
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45. PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex.

Author

He, Shanshan, Ni, Duojiao, Ma, Binyun, Lee, Joo-Hyung, Zhang, Tian, Ghozalli, Irene, Pirooz, Sara, Zhao, Zhen, Bharatham, Nagakumar, Li, Baihong, Oh, Soohwan, Takahashi, Yoshinori, Wang, Hong-Gang, Minassian, Arlet, Feng, Pinghui, Deretic, Vojo, Pepperkok, Rainer, Tagaya, Mitsuo, Yoon, Ho, Liang, Chengyu, and Lee, Wen-Hwa

Subjects
Amino Acid Sequence, Animals, Apoptosis Regulatory Proteins, Autophagy, Autophagy-Related Proteins, Beclin-1, Biological Transport, COS Cells, Cell Line, Cells, Cultured, Endoplasmic Reticulum, Golgi Apparatus, HEK293 Cells, HeLa Cells, Humans, Membrane Proteins, Mice, Models, Molecular, Molecular Sequence Data, Phosphatidylinositols, Protein Binding, Protein Structure, Tertiary, Sequence Alignment, Tumor Suppressor Proteins, Vesicular Transport Proteins
Abstract

Endoplasmic reticulum (ER)-Golgi membrane transport and autophagy are intersecting trafficking pathways that are tightly regulated and crucial for homeostasis, development and disease. Here, we identify UVRAG, a beclin-1-binding autophagic factor, as a phosphatidylinositol-3-phosphate (PtdIns(3)P)-binding protein that depends on PtdIns(3)P for its ER localization. We further show that UVRAG interacts with RINT-1, and acts as an integral component of the RINT-1-containing ER tethering complex, which couples phosphoinositide metabolism to COPI-vesicle tethering. Displacement or knockdown of UVRAG profoundly disrupted COPI cargo transfer to the ER and Golgi integrity. Intriguingly, autophagy caused the dissociation of UVRAG from the ER tether, which in turn worked in concert with the Bif-1-beclin-1-PI(3)KC3 complex to mobilize Atg9 translocation for autophagosome formation. These findings identify a regulatory mechanism that coordinates Golgi-ER retrograde and autophagy-related vesicular trafficking events through physical and functional interactions between UVRAG, phosphoinositide and their regulatory factors, thereby ensuring spatiotemporal fidelity of membrane trafficking and maintenance of organelle homeostasis.

Published
2013

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