A Beilina, IN Rudenko, A Kaganovich, L Civiero, H Chau, SK Kalia, LV Kalia, E Lobbestael, R Chia, K Ndukwe, J Ding, MA Nalls, International Parkinson’s Disease Genomics Consortium, North American Brain Expression Consortium, M Olszewski, DN Hauser, R Kumaran, AM Lozano, V Baekelandt, LE Greene, J-M Taymans, E Greggio, MR Cookson
Proc Natl Acad Sci U S A
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.