Journal Article

DZNE-2021-00606

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease.

Beilina, A. ; Rudenko, I. N. ; Kaganovich, A. ; Civiero, L. ; Chau, H. ; Kalia, S. K. ; Kalia, L. V. ; Lobbestael, E. ; Chia, R. ; Ndukwe, K. ; Ding, J. ; Nalls, M. A. ; Consortium, I. P. D. G. (Collaboration Author) ; Consortium, N. A. B. E. ; Olszewski, M. ; Hauser, D. N. ; Kumaran, R. ; Lozano, A. M. ; Baekelandt, V. ; Greene, L. E. ; Taymans, J.-M. ; Greggio, E. ; Cookson, M. R. ; Nalls, M. A. ; Plagnol, V. ; Hernandez, D. G.Extern* ; Sharma, M.Extern* ; Sheerin, U.-M. ; Saad, M. ; Simón-Sánchez, J. ; Schulte, C.Extern* ; Lesage, S. ; Sveinbjörnsdóttir, S. ; Arepalli, S. ; Barker, R. ; Ben-Shlomo, Y. ; Berendse, H. W. ; Berg, D.Extern* ; Bhatia, K. ; de Bie, R. M. A. ; Biffi, A. ; Bloem, B. ; Bochdanovits, Z. ; Bonin, M. ; Bras, J. M. ; Brockmann, K.Extern* ; Brooks, J. ; Burn, D. J. ; Charlesworth, G. ; Chen, H. ; Chinnery, P. F. ; Chong, S. ; Clarke, C. E. ; Cookson, M. R. ; Cooper, J. M. ; Corvol, J. C. ; Counsell, C. ; Damier, P. ; Dartigues, J.-F. ; Deloukas, P. ; Deuschl, G.Extern* ; Dexter, D. T. ; van Dijk, K. D. ; Dillman, A. ; Durif, F. ; Dürr, A.Extern* ; Edkins, S. ; Evans, J. R. ; Foltynie, T. ; Gao, J. ; Gardner, M. ; Gibbs, J. R. ; Goate, A. ; Gray, E. ; Guerreiro, R. ; Gústafsson, Ó. ; Harris, C. ; van Hilten, J. J. ; Hofman, A. ; Hollenbeck, A. ; Holton, J. ; Hu, M. ; Huang, X. ; Huber, H.Extern* ; Hudson, G. ; Hunt, S. E. ; Huttenlocher, J.Extern* ; Illig, T. ; Jónsson, P. V. ; Lambert, J.-C. ; Langford, C. ; Lees, A. ; Lichtner, P. ; Limousin, P. ; Lopez, G. ; Lorenz, D. ; McNeill, A. ; Moorby, C. ; Moore, M. ; Morris, H. R. ; Morrison, K. E. ; Mudanohwo, E. ; O'Sullivan, S. S. ; Pearson, J. ; Perlmutter, J. S. ; Pétursson, H. ; Pollak, P. ; Post, B. ; Potter, S. ; Ravina, B. ; Revesz, T. ; Riess, O. ; Rivadeneira, F. ; Rizzu, P.Extern* ; Ryten, M. ; Sawcer, S. ; Schapira, A. ; Scheffer, H. ; Shaw, K. ; Shoulson, I. ; Sidransky, E. ; Smith, C. ; Spencer, C. C. A. ; Stefánsson, H. ; Steinberg, S. ; Stockton, J. D. ; Strange, A. ; Talbot, K. ; Tanner, C. M. ; Tashakkori-Ghanbaria, A. ; Tison, F. ; Trabzuni, D. ; Traynor, B. J. ; Uitterlinden, A. G. ; Velseboer, D. ; Vidailhet, M. ; Walker, R. ; van de Warrenburg, B. ; Wickremaratchi, M. ; Williams, N. ; Williams-Gray, C. H. ; Winder-Rhodes, S. ; Stefánsson, K. ; Martinez, M. ; Hardy, J. ; Heutink, P.Extern* ; Brice, A. ; Gasser, T.Extern* ; Singleton, A. B. ; Wood, N. W. ; Arepalli, S. ; Cookson, M. R. ; Dillman, A. ; Ferrucci, L. ; Gibbs, J. R. ; Hernandez, D. G.Extern* ; Johnson, R. ; Longo, D. L. ; Majounie, E. ; Nalls, M. A. ; O'Brien, R. ; Singleton, A. B. ; Traynor, B. J. ; Troncoso, J. ; van der Brug, M. ; Zielke, H. R. ; Zonderman, A. B.

2014
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: doi:10.1073/pnas.1318306111

Abstract: 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.

Keyword(s): Adaptor Proteins, Signal Transducing: metabolism (MeSH) ; Analysis of Variance (MeSH) ; Blotting, Western (MeSH) ; Brain: metabolism (MeSH) ; Cell Fractionation (MeSH) ; DNA Primers: genetics (MeSH) ; Genetic Loci: genetics (MeSH) ; Genetic Predisposition to Disease: genetics (MeSH) ; Genome-Wide Association Study: methods (MeSH) ; Golgi Apparatus: ultrastructure (MeSH) ; HEK293 Cells (MeSH) ; Humans (MeSH) ; Immunoprecipitation (MeSH) ; Intracellular Signaling Peptides and Proteins: metabolism (MeSH) ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (MeSH) ; Mass Spectrometry (MeSH) ; Microscopy, Confocal (MeSH) ; Multiprotein Complexes: genetics (MeSH) ; Multiprotein Complexes: metabolism (MeSH) ; Parkinson Disease: enzymology (MeSH) ; Plasmids: genetics (MeSH) ; Protein Interaction Mapping: methods (MeSH) ; Protein-Serine-Threonine Kinases: genetics (MeSH) ; Protein-Serine-Threonine Kinases: metabolism (MeSH) ; Transport Vesicles: metabolism (MeSH) ; rab GTP-Binding Proteins: metabolism (MeSH) ; BAG5 ; GAK ; autophagy ; trans-Golgi ; Adaptor Proteins, Signal Transducing ; BAG5 protein, human ; DNA Primers ; Intracellular Signaling Peptides and Proteins ; Multiprotein Complexes ; rab7 protein ; GAK protein, human ; LRRK2 protein, human ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ; Protein-Serine-Threonine Kinases ; rab GTP-Binding Proteins

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