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 language | English (US) |
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Article number | jcs212324 |
Journal | Journal of cell science |
Volume | 131 |
Issue number | 9 |
DOIs | |
State | Published - May 1 2018 |
Externally published | Yes |
Keywords
- Arl13b
- Axoneme
- Ciliary membrane
- Ciliopathies
- Joubert syndrome
- Primary cilia
- Small GTPase
- Tubulin
ASJC Scopus subject areas
- Cell Biology