1. Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease
- Author
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Mina Ryten, Daniah Trabzuni, J. Ding, Bart Post, Albert Hofman, Jean-Charles Lambert, Olaf Riess, Michele T.M. Hu, Andrew B. Singleton, Stephen Sawcer, X. Huang, Caroline H. Williams-Gray, H. R. Zielke, C Smith, Peter Lichtner, B.P.C. van de Warrenburg, Bernard Ravina, F. Durif, Ellen Sidransky, Mike A. Nalls, Karen E. Morrison, J. R. Gibbs, Robert L. Johnson, Peter Heutink, David J. Burn, Michael Bonin, Sarah Edkins, T. Gasser, Luigi Ferrucci, H. Chau, Sampath Arepalli, Chris C. A. Spencer, Yoav Ben-Shlomo, Honglei Chen, Caroline M. Tanner, Zoltán Bochdanovits, Ruth Chia, Heiko Huber, Kari Stefansson, Dena G. Hernandez, Jean-Marc Taymans, Veerle Baekelandt, Iakov N. Rudenko, Evy Lobbestael, Huw R. Morris, A. Goate, C. Moorby, Lois E. Greene, Manu Sharma, Emma Gray, Ira Shoulson, Janet Brooks, Juan C. Troncoso, K. Shaw, Laura Civiero, Alessandra Biffi, Hans Scheffer, Matthew Moore, Alan B. Zonderman, S. Sveinbjornsdottir, Avazeh Tashakkori-Ghanbaria, Jean-Christophe Corvol, Vincent Plagnol, H. Petursson, Alice Kaganovich, M M Wickremaratchi, Nigel Williams, Thomas Foltynie, Henk W. Berendse, P. Damier, A. Strange, J. M. Cooper, Simon C. Potter, Patricia Limousin, Jiali Gao, Sophie Winder-Rhodes, M. Van Der Brug, Marie Vidailhet, Elisa Greggio, Nicholas W. Wood, Kevin Talbot, M. R. Cookson, Johanna Huttenlocher, J.J. van Hilten, Dan L. Longo, Alisdair McNeill, François Tison, K.D. van Dijk, David N. Hauser, Allissa Dillman, Suneil K. Kalia, Lorraine V. Kalia, Patrick F. Chinnery, Alexis Brice, Kelechi Ndukwe, J. F. Dartigues, M. Gardner, Mohamad Saad, Palmi V. Jonsson, Kailash P. Bhatia, Roger A. Barker, André G. Uitterlinden, Maria Martinez, R. Walker, Elisa Majounie, Fernando Rivadeneira, Joel S. Perlmutter, Panagiotis Deloukas, Bryan J. Traynor, Ese E. Mudanohwo, Grisel Lopez, UM Sheerin, Joanne D. Stockton, Thomas Illig, Andres M. Lozano, Rita Guerreiro, David T. Dexter, Andrew J. Lees, Sean Chong, Gavin Hudson, Cordelia Langford, Günther Deuschl, Ravindran Kumaran, Janice L. Holton, Tamas Revesz, B.R. Bloem, Alexandra Beilina, Clare Elizabeth Harris, Daniela Berg, Anthony H.V. Schapira, Suzanne Lesage, Sean S. O'Sullivan, Albert R. Hollenbeck, James A. Pearson, R. M. A. de Bie, Delia Lorenz, Sarah E. Hunt, Richard O'Brien, Gavin Charlesworth, Maciej B. Olszewski, Stacy Steinberg, Kathrin Brockmann, Carl E Clarke, Patrizia Rizzu, Claudia Schulte, Hreinn Stefansson, Daan C. Velseboer, Omar Gustafsson, Jonathan R. Evans, Alexandra Durr, Javier Simón-Sánchez, Pierre Pollak, H. Z. Munchen, Jose Bras, Carl Counsell, John Hardy, ANS - Amsterdam Neuroscience, Neurology, and Graduate School
- Subjects
Candidate gene ,autophagy ,Blotting, Western ,Golgi Apparatus ,Genome-wide association study ,Protein Serine-Threonine Kinases ,Biology ,Leucine-rich repeat ,Cell Fractionation ,Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ,Mass Spectrometry ,Commentaries ,Protein Interaction Mapping ,Humans ,Immunoprecipitation ,Genetic Predisposition to Disease ,Transport Vesicles ,Gene ,Adaptor Proteins, Signal Transducing ,DNA Primers ,Genetics ,Analysis of Variance ,Microscopy, Confocal ,Multidisciplinary ,Kinase ,HEK 293 cells ,BAG5 ,Intracellular Signaling Peptides and Proteins ,Brain ,rab7 GTP-Binding Proteins ,Signal transducing adaptor protein ,Parkinson Disease ,Biological Sciences ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,GAK ,LRRK2 ,nervous system diseases ,HEK293 Cells ,Genetic Loci ,rab GTP-Binding Proteins ,Multiprotein Complexes ,trans-Golgi ,Genome-Wide Association Study ,Plasmids - Abstract
Item does not contain fulltext Mutations in leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson disease (PD), and common variants around LRRK2 are a risk factor for sporadic PD. Using protein-protein interaction arrays, we identified BCL2-associated athanogene 5, Rab7L1 (RAB7, member RAS oncogene family-like 1), and Cyclin-G-associated kinase as binding partners of LRRK2. The latter two genes are candidate genes for risk for sporadic PD identified by genome-wide association studies. These proteins form a complex that promotes clearance of Golgi-derived vesicles through the autophagy-lysosome system both in vitro and in vivo. We propose that three different genes for PD have a common biological function. More generally, data integration from multiple unbiased screens can provide insight into human disease mechanisms.
- Published
- 2014
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