PT - JOURNAL ARTICLE AU - Yan-Xia Liu AU - Wei-Yue Sun AU - Bin Xue AU - Rui-Kai Zhang AU - Wen-Juan Li AU - Xixian Xie AU - Zhen-Chuan Fan TI - ARL3 Mediates BBSome Ciliary Turnover by Promoting Its Outward Diffusion through the Transition Zone AID - 10.1101/2021.11.19.469163 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.11.19.469163 4099 - http://biorxiv.org/content/early/2021/11/19/2021.11.19.469163.short 4100 - http://biorxiv.org/content/early/2021/11/19/2021.11.19.469163.full AB - Ciliary receptors and their certain downstream signaling components undergo intraflagellar transport (IFT) as BBSome cargoes to maintain their ciliary dynamics for sensing and transducing extracellular stimuli inside the cell. Cargo laden BBSomes shed from retrograde IFT at the proximal ciliary region above the transition zone (TZ) followed by diffusing through the TZ for ciliary retrieval, while how the BBSome barrier passage is controlled remains elusive. Here, we show that the BBSome is a major effector of the Arf-like 3 (ARL3) GTPase in Chlamydomonas. Under physiological condition, ARL3GDP binds the membrane for diffusing into and residing in cilia. Following a nucleotide conversion, ARL3GTP dissociates with the ciliary membrane and binds and recruits the IFT-detached and cargo (phospholipase D, PLD)-laden BBSome at the proximal ciliary region to diffuse through the TZ and out of cilia. ARL3 deficiency impairs ciliary signaling, e.g. phototaxis of Chlamydomonas cells, by disrupting BBSome ciliary retrieval, providing a mechanistic understanding behind BBSome ciliary turnover required for ciliary signaling.Competing Interest StatementThe authors have declared no competing interest.