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Updated: Aug 28, 2025

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag
Published on: December 14, 2017
LRRK2 phosphorylation of Rab GTPases in Parkinson's disease
1Department of Biochemistry, Stanford University School of Medicine, CA, USA.
Abstract:
Rab GTPases comprise a large family of conserved GTPases that are critical regulators of the secretory and endocytic pathways. The human genome encodes ~ 65 Rabs that localize to discrete membrane compartments and, when in their GTP-bound state, bind to effector proteins to carry out diverse functions. Activating mutations in LRRK2 kinase cause Parkinson's disease, and subsets of Rab GTPases are important LRRK2 substrates. LRRK2 phosphorylates a conserved threonine residue that is essential for Rab interaction with guanine nucleotide exchange factors, effectors, and GDI that recycles Rabs between membrane compartments. This brief review will highlight new findings related to LRRK2-mediated phosphorylation of Rab GTPases and its consequences. Remarkably, Rab phosphorylation flips a switch on Rab effector selection with dominant consequences for cell pathophysiology.
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