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Updated: Jun 18, 2025

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag
Published on: December 14, 2017
Mechanisms of lysosomal tubulation and sorting driven by LRRK2
Luis Bonet-Ponce1, Jillian H Kluss2, Mark R Cookson3
1Department of Neurology, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, U.S.A.
Abstract:
Lysosomes are dynamic cellular structures that adaptively remodel their membrane in response to stimuli, including membrane damage. Lysosomal dysfunction plays a central role in the pathobiology of Parkinson's disease (PD). Gain-of-function mutations in Leucine-rich repeat kinase 2 (LRRK2) cause familial PD and genetic variations in its locus increase the risk of developing the sporadic form of the disease. We previously uncovered a process we term LYTL (LYsosomal Tubulation/sorting driven by LRRK2), wherein membrane-damaged lysosomes generate tubules sorted into mobile vesicles. Subsequently, these vesicles interact with healthy lysosomes. LYTL is orchestrated by LRRK2 kinase activity, via the recruitment and phosphorylation of a subset of RAB GTPases. Here, we summarize the current understanding of LYTL and its regulation, as well as the unknown aspects of this process.
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