The Parkinson’s Disease Protein LRRK2 Interacts with the GARP Complex to Promote Retrograde Transport to the trans-Golgi Network

• DOI: 10.1016/j.celrep.2020.107614
• Publication Date: 2020-05-05T14:40:36Z
• Authors: Alexandra Beilina; Luis Bonet-Ponce; Ravindran Kumaran; Jennifer J. Kordich; Morié Ishida; Adamantios Mamais; Alice Kaganovich; Sara Saez-Atienzar; David C. Gershlick; Dorien A. Roosen; Laura Pellegrini; Vlad Malkov; Matthew J. Fell; Kirsten Harvey; Juan S. Bonifacino; Darren J. Moore; Mark R. Cookson
• Keywords: LRRK2; Transport protein; Axoplasmic transport; Intracellular transport

Mutations in Leucine-rich repeat kinase 2 (LRRK2) cause Parkinson's disease (PD). However, the precise function of LRRK2 remains unclear. We report an interaction between and VPS52, a subunit Golgi-associated retrograde protein (GARP) complex that identifies regulating membrane fusion at trans-Golgi network (TGN). At TGN, further interacts with Golgi SNAREs VAMP4 Syntaxin-6 acts as scaffolding platform stabilizes GARP-SNAREs formation. Therefore, influences both post-Golgi trafficking pathways manner dependent on its GTP binding activity. This action is exaggerated by mutations associated can be blocked inhibitors. Disruption GARP sensitizes dopamine neurons to mutant toxicity C. elegans, showing these are interlinked vivo suggesting link PD.