Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease

Research output: Contribution to journalArticle

Authors

  • Alexandria Beilina
  • Iakov N Rudenko
  • Alice Kaganovich
  • Laura Civiero
  • Hien Chau
  • Suneil K Kalia
  • Lorraine V Kalia
  • Evy Lobbestael
  • Ruth Chia
  • Kelechi Ndukwe
  • Jinhui Ding
  • Mike A Nalls
  • Maciej Olszewski
  • David N Hauser
  • Ravindran Kumaran
  • Andres M Lozano
  • Veerle Baekelandt
  • Lois E Greene
  • Jean-Marc Taymans
  • Elisa Greggio
  • Mark R Cookson
  • International Parkinson's Disease Genomics Consortium (IPDGC)
  • Karen Morrison

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)2626-31
Number of pages6
JournalNational Academy of Sciences. Proceedings
Volume111
Issue number7
Publication statusPublished - 18 Feb 2014

Keywords

  • Adaptor Proteins, Signal Transducing, Analysis of Variance, Blotting, Western, Brain, Cell Fractionation, DNA Primers, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Golgi Apparatus, HEK293 Cells, Humans, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Mass Spectrometry, Microscopy, Confocal, Multiprotein Complexes, Parkinson Disease, Plasmids, Protein Interaction Mapping, Protein-Serine-Threonine Kinases, Transport Vesicles, rab GTP-Binding Proteins