LRRK1-mediated NDEL1 phosphorylation promotes cilia disassembly via dynein-2-driven retrograde intraflagellar transport

Hiroshi Hanafusa, Shin Kedashiro, Mako Gotoh, Ko Hei Saitoh, Hironori Inaba, Tomoki Nishioka, Kozo Kaibuchi, Masaki Inagaki, Naoki Hisamoto, Kunihiro Matsumoto

Research output: Contribution to journalArticlepeer-review

Abstract

Primary cilia are antenna-like organelles that regulate growth and development via extracellular signals. However, the molecular mechanisms underlying cilia dynamics, particularly those regulating their disassembly, are not well understood. Here, we show that leucine-rich repeat kinase 1 (LRRK1) plays a role in regulating cilia disassembly. The depletion of LRRK1 impairs primary cilia resorption following serum stimulation in cultured cells. Polo-like kinase 1 (PLK1) plays an important role in this process. During ciliary resorption, PLK1 phosphorylates LRRK1 at the primary cilia base, resulting in its activation. We identified nuclear distribution protein nudE-like 1 (NDEL1), which is known to positively regulate cilia disassembly, as a target of LRRK1 phosphorylation. Whereas LRRK1 phosphorylation of NDEL1 on Ser-155 promotes NDEL1 interaction with the intermediate chains of cytoplasmic dynein-2, it is also crucial for triggering ciliary resorption through dynein-2-driven retrograde intraflagellar transport. These findings provide evidence that a novel PLK1-LRRK1-NDEL1 pathway regulates cilia disassembly.

Original languageEnglish
Article numberjcs259999
JournalJournal of cell science
Volume135
Issue number21
DOIs
Publication statusPublished - 11-2022

All Science Journal Classification (ASJC) codes

  • Cell Biology

Fingerprint

Dive into the research topics of 'LRRK1-mediated NDEL1 phosphorylation promotes cilia disassembly via dynein-2-driven retrograde intraflagellar transport'. Together they form a unique fingerprint.

Cite this