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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-\u0394GD) or whose GTPase domain is inactivated (ARL13B-T35N) retain ciliary localization, but fail to rescue ciliogenesis defects of null Arl13bhnn mouse embryonic fibroblasts (MEFs). However, while ARL13B-\u0394GD 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.<\/jats:p>","DOI":"10.1242\/jcs.212324","type":"journal-article","created":{"date-parts":[[2018,3,28]],"date-time":"2018-03-28T09:10:27Z","timestamp":1522228227000},"source":"Crossref","is-referenced-by-count":30,"title":["The Joubert syndrome protein ARL13B binds tubulin to maintain uniform distribution of proteins along the ciliary membrane"],"prefix":"10.1242","volume":"131","author":[{"given":"Ekaterina","family":"Revenkova","sequence":"first","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai 1 Department of Ophthalmology , , One Gustave L. Levy Place, New York, NY 10029 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Liu","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai 1 Department of Ophthalmology , , One Gustave L. Levy Place, New York, NY 10029 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Luca","family":"Gusella","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai 2 Department of Medicine , , One Gustave L. Levy Place, New York, NY 10029 , USA"},{"name":"Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai 3 , One Gustave L. Levy Place, New York, NY 10029 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6483-9540","authenticated-orcid":false,"given":"Carlo","family":"Iomini","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai 1 Department of Ophthalmology , , One Gustave L. Levy Place, New York, NY 10029 , USA"},{"name":"Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai 3 , One Gustave L. Levy Place, New York, NY 10029 , USA"},{"name":"Icahn School of Medicine at Mount Sinai 4 Department of Cell, Developmental and Regenerative Biology , , One Gustave L. Levy Place, New York, NY 10029 , USA"},{"name":"Friedman Brain Institute, Icahn School of Medicine at Mount Sinai 5 , One Gustave L. Levy Place, New York, NY 10029 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2018,5,4]]},"reference":[{"key":"2024061318120096000_JCS212324C1","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/B978-0-12-397945-2.00019-6","article-title":"Reconstitution of flagellar sliding","volume":"524","author":"Alper","year":"2013","journal-title":"Methods Enzymol."},{"key":"2024061318120096000_JCS212324C2","doi-asserted-by":"publisher","first-page":"21354","DOI":"10.1073\/pnas.1218272110","article-title":"Arl13b regulates endocytic recycling traffic","volume":"109","author":"Barral","year":"2012","journal-title":"Proc. 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