Related Experiment Video

Updated: Feb 19, 2026

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag
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Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag

Published on: December 14, 2017

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Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis

Martin Steger1, Federico Diez2, Herschel S Dhekne3

  • 1Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried, Germany.

Elife
|November 11, 2017
PubMed

Insights

Parkinson's disease kinase LRRK2 phosphorylates specific Rab GTPases. This impacts primary cilia formation, suggesting Rab defects contribute to LRRK2-related pathologies.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Molecular Biology

Background:

  • Parkinson's disease (PD) is linked to mutations in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene.
  • LRRK2 is known to phosphorylate specific Rab GTPases, proteins involved in intracellular transport.

Purpose of the Study:

  • To systematically analyze the Rab protein family for LRRK2 phosphorylation targets.
  • To investigate the role of LRRK2-mediated Rab phosphorylation in primary ciliogenesis.

Main Methods:

  • Systematic analysis of the Rab protein family using mass spectrometry.
  • Affinity enrichment mass spectrometry to identify interacting proteins.
  • Analysis of ciliogenesis in fibroblasts from LRRK2-mutant mice.

Main Results:

  • Identified 14 Rab GTPases phosphorylated by LRRK2, with evidence for endogenous phosphorylation in ten.
  • Discovered that RILPL1 and RILPL2 specifically interact with LRRK2-phosphorylated Rab GTPases (Rab8A, Rab10, Rab12).
  • Demonstrated a reduction in primary cilia formation in cells with pathogenic LRRK2 mutations.

Conclusions:

  • LRRK2 plays a role in regulating primary ciliogenesis.
  • Defects in Rab-mediated transport or signaling at cilia may underlie LRRK2-dependent pathologies in Parkinson's disease.
Keywords:
LRRK2Parkinson's diseaseRab GTPasesbiochemistryciliogenesishumanmass spectrometrymouseproteomics

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