The Joubert syndrome protein ARL13B binds tubulin to maintain uniform distribution of proteins along the ciliary membrane

Ekaterina Revenkova, Qing Liu, G. Luca Gusella, Carlo Iomini

Research output: Contribution to journalArticlepeer-review

Abstract

Cilia-mediated signal transduction involves precise targeting and localization of selected molecules along the ciliary membrane. However, the molecular mechanism underlying these events is unclear. The Joubert syndrome protein ARL13B is a membraneassociated G-protein that localizes along the cilium and functions in protein transport and signaling. We identify tubulin as a direct interactor of ARL13B and demonstrate that the association occurs via the G-domain and independently from the GTPase activity of ARL13B. The G-domain is necessary for the interaction of ARL13B with the axoneme both in vitro and in vivo. We further show that exogenously expressed mutants lacking the tubulin-binding G-domain (ARL13B-ΔGD) or whose GTPase domain is inactivated (ARL13BT35N) retain ciliary localization, but fail to rescue ciliogenesis defects of null Arl13bhnn mouse embryonic fibroblasts (MEFs). However, while ARL13B-ΔGD and the membrane proteins Smoothened (SMO) and Somatostatin receptor-3 (SSTR3) distribute unevenly along the cilium of Arl13bhnn MEFs, ARL13B-T35N distributes evenly along the cilium and enables the uniform distribution of SMO and SSTR3. Thus, we propose a so far unknown function of ARL13B in anchoring ciliary membrane proteins to the axoneme through the direct interaction of its G-domain with tubulin.

Original languageEnglish (US)
Article numberjcs212324
JournalJournal of cell science
Volume131
Issue number9
DOIs
StatePublished - May 1 2018

Keywords

  • Arl13b
  • Axoneme
  • Ciliary membrane
  • Ciliopathies
  • Joubert syndrome
  • Primary cilia
  • Small GTPase
  • Tubulin

ASJC Scopus subject areas

  • Cell Biology

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