Insights into the cellular consequences of LRRK2-mediated Rab protein phosphorylation. (26th April 2023)

• Record Type: Journal Article
• Authors: Fasiczka, Rachel; Naaldijk, Yahaira; Brahmia, Besma; Hilfiker, Sabine
• Is Part Of: Biochemical Society transactions. Volume 51:Number 2(2023)
• Page Start: 587
• Page End: 595
• Publication Date: 2023-04-26
• Subjects: ciliogenesis -- LRRK2 -- lysosome -- Parkinson's disease -- phosphorylation/dephosphorylation -- Rab protein; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST20201145
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : Point mutations in leucine-rich repeat kinase 2 (LRRK2) which cause Parkinson's disease increase its kinase activity, and a subset of Rab GTPases have been identified as endogenous LRRK2 kinase substrates. Their phosphorylation correlates with a loss-of-function for the membrane trafficking steps they are normally involved in, but it also allows them to bind to a novel set of effector proteins with dominant cellular consequences. In this brief review, we will summarize novel findings related to the LRRK2-mediated phosphorylation of Rab GTPases and its various cellular consequences in vitro and in the intact brain, and we will highlight major outstanding questions in the field.