LRRK2-phosphorylated Rab10 sequesters Myosin Va with RILPL2 during ciliogenesis blockade

Herschel S. Dhekne, Izumi Yanatori, Edmundo G. Vides, Yuriko Sobu, Federico Diez, Francesca Tonelli, Suzanne R. Pfeffer (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)
111 Downloads (Pure)


Activating mutations in LRRK2 kinase causes Parkinson’s disease. Pathogenic LRRK2 phosphorylates a subset of Rab GTPases and blocks ciliogenesis. Thus, defining novel phospho-Rab interacting partners is critical to our understanding of the molecular basis of LRRK2 pathogenesis. RILPL2 binds with strong preference to LRRK2-phosphorylated Rab8A and Rab10. RILPL2 is a binding partner of the motor protein and Rab effector, Myosin Va. We show here that the globular tail domain of Myosin Va also contains a high affinity binding site for LRRK2-phosphorylated Rab10. In the presence of pathogenic LRRK2, RILPL2 and MyoVa relocalize to the peri-centriolar region in a phosphoRab10-dependent manner. PhosphoRab10 retains Myosin Va over pericentriolar membranes as determined by fluorescence loss in photobleaching microscopy. Without pathogenic LRRK2, RILPL2 is not essential for ciliogenesis but RILPL2 over-expression blocks ciliogenesis in RPE cells independent of tau tubulin kinase recruitment to the mother centriole. These experiments show that LRRK2 generated-phosphoRab10 dramatically redistributes a significant fraction of Myosin Va and RILPL2 to the mother centriole in a manner that likely interferes with Myosin Va’s role in ciliogenesis.
Original languageEnglish
Article numbere202101050
Number of pages16
JournalLife Science Alliance
Issue number5
Early online date16 Mar 2021
Publication statusPublished - May 2021


  • LRRK2
  • Parkinson’s disease
  • Primary Cilia
  • Rab GTPase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Health, Toxicology and Mutagenesis
  • Plant Science
  • Ecology


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