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RABL2 Activates ARL3 as an ARL3 GEF for Removing Signaling Proteins out of Cilia via the BBSome

ABSTRACT: Certain ciliary transmembrane and membrane-associated signaling proteins export from cilia as BBSome cargoes via the outward BBSome transition zone (TZ) diffusion pathway. Murine Rab-like 2 (Rabl2) GTPase resembles Chlamydomonas Arf-like 3 (ARL3) GTPase in promoting outward BBSome TZ passage, while how they crosstalk in this event remain elusive. Here, we report that Chlamydomonas RABL2 in a GTP-bound form (RABL2GTP) cycles through cilia via IFT as an IFT-B1 cargo, dissociates from retrograde IFT trains at the TZ region, and converts to RABL2GDP for activating ARL3GDP as an ARL3 guanine nucleotide exchange factor. This confers ARL3GTP to detach from the ciliary membrane and become available for recruiting the phospholipase D-laden BBSome, autonomous of retrograde IFT, to diffuse through the TZ for ciliary retrieval. RABL2GDP then exits cilia by binding ARL3GTP/BBSome as a BBSome cargo. Our data identify ciliary signaling proteins export from cilia via the RABL2-ARL3 pair-mediated outward BBSome TZ diffusion pathway. If this holds true in humans, hedgehog signaling defect-induced Bardet-Biedl syndrome caused by RABL2 and ARL3 mutations could be well explained in a mutation-specific manner.

ORGANISM(S): Chlamydomonas reinhardtii

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PROVIDER: S-BSST978 | biostudies-other |

REPOSITORIES: biostudies-other

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