| First Author | Revenkova E | Year | 2018 |
| Journal | J Cell Sci | Volume | 131 |
| Issue | 9 | PubMed ID | 29592971 |
| Mgi Jnum | J:261450 | Mgi Id | MGI:6155345 |
| Doi | 10.1242/jcs.212324 | Citation | Revenkova E, et al. (2018) The Joubert syndrome protein ARL13B binds tubulin to maintain uniform distribution of proteins along the ciliary membrane. J Cell Sci 131(9):jcs212324 |
| abstractText | 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 membrane-associated 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-DeltaGD) or whose GTPase domain is inactivated (ARL13B-T35N) retain ciliary localization, but fail to rescue ciliogenesis defects of null Arl13b(hnn) mouse embryonic fibroblasts (MEFs). However, while ARL13B-DeltaGD and the membrane proteins Smoothened (SMO) and Somatostatin receptor-3 (SSTR3) distribute unevenly along the cilium of Arl13b(hnn) 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. |
