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3. Disruption of intraflagellar protein transport in photoreceptor cilia causes Leber congenital amaurosis in humans and mice

Author

Boldt, Karsten, Mans, Dorus A., Won, Jungyeon, van Reeuwijk, Jeroen, Vogt, Andreas, Kinkl, Norbert, Letteboer, Stef J.F., Hicks, Wanda L., Hurd, Ron E., Naggert, Jurgen K., Texier, Yves, den Hollander, Anneke I., Koenekoop, Robert K., Bennett, Jean, Cremers, Frans P.M., Gloeckner, Christian J., Nishina, Patsy M., Roepman, Ronald, and Ueffing, Marius

Subjects
Blindness, Genetic disorders, Health care industry
Abstract

The mutations that cause Leber congenital amaurosis (LCA) lead to photoreceptor cell death at an early age, causing childhood blindness. To unravel the molecular basis of LCA, we analyzed how [...]

Published
2011
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5. CiliaCarta: An integrated and validated compendium of ciliary genes

Author

van Dam, Teunis J. P., primary, Kennedy, Julie, additional, van der Lee, Robin, additional, de Vrieze, Erik, additional, Wunderlich, Kirsten A., additional, Rix, Suzanne, additional, Dougherty, Gerard W., additional, Lambacher, Nils J., additional, Li, Chunmei, additional, Jensen, Victor L., additional, Leroux, Michel R., additional, Hjeij, Rim, additional, Horn, Nicola, additional, Texier, Yves, additional, Wissinger, Yasmin, additional, van Reeuwijk, Jeroen, additional, Wheway, Gabrielle, additional, Knapp, Barbara, additional, Scheel, Jan F., additional, Franco, Brunella, additional, Mans, Dorus A., additional, van Wijk, Erwin, additional, Képès, François, additional, Slaats, Gisela G., additional, Toedt, Grischa, additional, Kremer, Hannie, additional, Omran, Heymut, additional, Szymanska, Katarzyna, additional, Koutroumpas, Konstantinos, additional, Ueffing, Marius, additional, Nguyen, Thanh-Minh T., additional, Letteboer, Stef J. F., additional, Oud, Machteld M., additional, van Beersum, Sylvia E. C., additional, Schmidts, Miriam, additional, Beales, Philip L., additional, Lu, Qianhao, additional, Giles, Rachel H., additional, Szklarczyk, Radek, additional, Russell, Robert B., additional, Gibson, Toby J., additional, Johnson, Colin A., additional, Blacque, Oliver E., additional, Wolfrum, Uwe, additional, Boldt, Karsten, additional, Roepman, Ronald, additional, Hernandez-Hernandez, Victor, additional, and Huynen, Martijn A., additional

Published
2019
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6. An organelle-specific protein landscape identifies novel diseases and molecular mechanisms

Author

Boldt, Karsten, van Reeuwijk, Jeroen, Dougherty, Gerard, Lamers, Ideke J C, Coene, Karlien L M, Arts, Heleen H, Betts, Matthew J, Beyer, Tina, Bolat, Emine, Gloeckner, Christian Johannes, Haidari, Khatera, Hetterschijt, Lisette, Lu, Qianhao, Iaconis, Daniela, Jenkins, Dagan, Klose, Franziska, Knapp, Barbara, Latour, Brooke, Letteboer, Stef J F, Marcelis, Carlo L, Mitic, Dragana, Morleo, Manuela, Oud, Machteld M, Koutroumpas, Konstantinos, Riemersma, Moniek, Rix, Susan, Terhal, Paulien A, Toedt, Grischa, van Dam, Teunis J P, de Vrieze, Erik, Wissinger, Yasmin, Wu, Ka Man, Apic, Gordana, Beales, Philip L, Nguyen, Thanh-Minh T, Blacque, Oliver E, Gibson, Toby J, Huynen, Martijn A, Katsanis, Nicholas, Kremer, Hannie, Omran, Heymut, van Wijk, Erwin, Wolfrum, Uwe, Kepes, François, Davis, Erica E, Texier, Yves, Franco, Brunella, Giles, Rachel H, Ueffing, Marius, Russell, Robert B, Roepman, Ronald, Group, UK10K Rare Diseases, Al-Turki, Saeed, Anderson, Carl, Antony, Dinu, Barroso, Inês, van Beersum, Sylvia E C, Bentham, Jamie, Bhattacharya, Shoumo, Carss, Keren, Chatterjee, Krishna, Cirak, Sebahattin, Cosgrove, Catherine, Danecek, Petr, Durbin, Richard, Fitzpatrick, David, Floyd, Jamie, Horn, Nicola, Reghan Foley, A., Franklin, Chris, Futema, Marta, Humphries, Steve E, Hurles, Matt, Joyce, Chris, McCarthy, Shane, Mitchison, Hannah M, Muddyman, Dawn, Muntoni, Francesco, Willer, Jason R, O'Rahilly, Stephen, Onoufriadis, Alexandros, Payne, Felicity, Plagnol, Vincent, Raymond, Lucy, Savage, David B, Scambler, Peter, Schmidts, Miriam, Schoenmakers, Nadia, Semple, Robert, Mans, Dorus A, Serra, Eva, Stalker, Jim, van Kogelenberg, Margriet, Vijayarangakannan, Parthiban, Walter, Klaudia, Whittall, Ros, Williamson, Kathy, Boldt, K, van Reeuwijk, J, Lu, Q, Koutroumpas, K, Nguyen, Tmt, Texier, Y, van Beersum, Sec, Horn, N, Willer, Jr, Mans, Da, Dougherty, G, Lamers, Ijc, Coene, Klm, Arts, Hh, Betts, Mj, Beyer, T, Bolat, E, Gloeckner, Cj, Haidari, K, Hetterschijt, L, Iaconis, D, Jenkins, D, Klose, F, Knapp, B, Latour, B, Letteboer, Sjf, Marcelis, Cl, Mitic, D, Morleo, M, Oud, Mm, Riemersma, M, Rix, S, Terhal, Pa, Toedt, G, van Dam, Tjp, de Vrieze, E, Wissinger, Y, Wu, Km, Apic, G, Beales, Pl, Blacque, Oe, Gibson, Tj, Huynen, Ma, Katsanis, N, Kremer, H, Omran, H, van Wijk, E, Wolfrum, U, Kepes, F, Davis, Ee, Franco, B, Giles, Rh, Ueffing, M, Russell, Rb, Roepman, R, Boldt, Karsten, Van Reeuwijk, Jeroen, Lu, Qianhao, Koutroumpas, Konstantino, Nguyen, Thanh Minh T., Texier, Yve, Van Beersum, Sylvia E. C., Horn, Nicola, Willer, Jason R., Mans, Dorus A., Dougherty, Gerard, Lamers, Ideke J. C., Coene, Karlien L. M., Arts, Heleen H., Betts, Matthew J., Beyer, Tina, Bolat, Emine, Gloeckner, Christian Johanne, Haidari, Khatera, Hetterschijt, Lisette, Iaconis, Daniela, Jenkins, Dagan, Klose, Franziska, Knapp, Barbara, Latour, Brooke, Letteboer, Stef J. F., Marcelis, Carlo L., Mitic, Dragana, Morleo, Manuela, Oud, Machteld M., Riemersma, Moniek, Rix, Susan, Terhal, Paulien A., Toedt, Grischa, Van Dam, Teunis J. P., De Vrieze, Erik, Wissinger, Yasmin, Wu, Ka Man, Al Turki, Saeed, Anderson, Carl, Antony, Dinu, Barroso, Inê, Bentham, Jamie, Bhattacharya, Shoumo, Carss, Keren, Chatterjee, Krishna, Cirak, Sebahattin, Cosgrove, Catherine, Danecek, Petr, Durbin, Richard, Fitzpatrick, David, Floyd, Jamie, Foley, A. Reghan, Franklin, Chri, Futema, Marta, Humphries, Steve E., Hurles, Matt, Joyce, Chri, Mccarthy, Shane, Mitchison, Hannah M., Muddyman, Dawn, Muntoni, Francesco, O'Rahilly, Stephen, Onoufriadis, Alexandro, Payne, Felicity, Plagnol, Vincent, Raymond, Lucy, Savage, David B., Scambler, Peter, Schmidts, Miriam, Schoenmakers, Nadia, Semple, Robert, Serra, Eva, Stalker, Jim, Van Kogelenberg, Margriet, Vijayarangakannan, Parthiban, Walter, Klaudia, Whittall, Ro, Williamson, Kathy, Apic, Gordana, Beales, Philip L., Blacque, Oliver E., Gibson, Toby J., Huynen, Martijn A., Katsanis, Nichola, Kremer, Hannie, Omran, Heymut, Van Wijk, Erwin, Wolfrum, Uwe, Kepes, Françoi, Davis, Erica E., Franco, Brunella, Giles, Rachel H., Ueffing, Mariu, Russell, Robert B., and Roepman, Ronald

Subjects
Proteomics, 0301 basic medicine, Systems Analysis, DNA Mutational Analysis, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], General Physics and Astronomy, Datasets as Topic, methods [Chromatography, Affinity], Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Chromatography, Affinity, Mass Spectrometry, Protein Interaction Mapping, therapy [Ciliopathies], genetics [Ciliopathies], methods [Molecular Targeted Therapy], Molecular Targeted Therapy, Protein Interaction Maps, Multidisciplinary, Cilium, Chemistry (all), abnormalities [Spine], pathology [Ciliopathies], genetics [Muscle Hypotonia], therapy [Muscle Hypotonia], Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], metabolism [Proteins], isolation & purification [Proteins], physiology [Biological Transport], 3. Good health, Cell biology, Vesicular transport protein, pathology [Dwarfism], metabolism [Cilia], Muscle Hypotonia, ddc:500, pathology [Muscle Hypotonia], pathology [Spine], genetics [Dwarfism], Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Science, Dwarfism, Exocyst, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Physics and Astronomy (all), 03 medical and health sciences, Intraflagellar transport, Ciliogenesis, Organelle, Humans, Cilia, Biochemistry, Genetics and Molecular Biology (all), Proteins, Biological Transport, General Chemistry, therapy [Dwarfism], Fibroblasts, genetics [Proteins], Ciliopathies, Spine, methods [Protein Interaction Mapping], Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], 030104 developmental biology, Proteostasis, HEK293 Cells, methods [Proteomics]
Abstract

Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine., Mutations in proteins that localize to primary cilia cause devastating diseases, yet the primary cilium is a poorly understood organelle. Here the authors use interaction proteomics to identify a network of human ciliary proteins that provides new insights into several biological processes and diseases.

Published
2016

7. Quantitative analysis of ciliary protein networks - Characterization of the intraflagellar transport complex B

Author

Texier, Yves Stephan, Hrabé de Angelis, Martin (Prof. Dr.), Adamski, Jerzy (Prof. Dr.), and Ueffing, Marius (Prof. Dr.)

Subjects
Biowissenschaften, Biologie, ddc:570
Abstract

The intraflagellar transport (IFT) complex is essential for ciliary transport. To gain insight into the function of the IFT complex, a method to determine its sub-structure was developed. The components of the IFT complex B (IFT-B) and its sub-structure were determined using different biochemical and mass spectrometric methods. Furthermore, the centrosomal protein 170 was identified to be associated to the IFT-B and shown to be essential for its ciliary localization. Der Intraflagellare Transport (IFT) Komplex ist essentiell für den ziliären Transport. Um mehr über die Funktion des IFT-Komplexes zu erfahren, wurde eine Methode zur Bestimmung seiner Sub-Struktur entwickelt. Unter Verwendung verschiedener biochemischer und massenspektrometrischer Methoden, wurden die Komponenten des IFT-Komplexes B (IFT-B) bestimmt, sowie seine Sub-Struktur analysiert. Des Weiteren wurde die Assoziation des Zentrosomalen Proteins 170 an den IFT-B, sowie die essentielle Funktion für dessen ziliäre Lokalisation gezeigt.

Published
2014

8. Heptad-Specific Phosphorylation of RNA Polymerase II CTD

Author

Schüller, Roland, primary, Forné, Ignasi, additional, Straub, Tobias, additional, Schreieck, Amelie, additional, Texier, Yves, additional, Shah, Nilay, additional, Decker, Tim-Michael, additional, Cramer, Patrick, additional, Imhof, Axel, additional, and Eick, Dirk, additional

Published
2016
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9. NINL and DZANK1 Co-function in Vesicle Transport and Are Essential for Photoreceptor Development in Zebrafish

Author

Dona, Margo, primary, Bachmann-Gagescu, Ruxandra, additional, Texier, Yves, additional, Toedt, Grischa, additional, Hetterschijt, Lisette, additional, Tonnaer, Edith L., additional, Peters, Theo A., additional, van Beersum, Sylvia E. C., additional, Bergboer, Judith G. M., additional, Horn, Nicola, additional, de Vrieze, Erik, additional, Slijkerman, Ralph W. N., additional, van Reeuwijk, Jeroen, additional, Flik, Gert, additional, Keunen, Jan E., additional, Ueffing, Marius, additional, Gibson, Toby J., additional, Roepman, Ronald, additional, Boldt, Karsten, additional, Kremer, Hannie, additional, and van Wijk, Erwin, additional

Published
2015
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