ARL3 mediates BBSome ciliary turnover by promoting its outward movement across the transition zone

Author:

Liu Yan-Xia1,Sun Wei-Yue1ORCID,Xue Bin1,Zhang Rui-Kai1,Li Wen-Juan1,Xie Xixian1ORCID,Fan Zhen-Chuan1ORCID

Affiliation:

1. State Key Laboratory of Food Nutrition and Safety, Institute of Health Biotechnology, Tianjin University of Science and Technology, Tianjin, China 1

Abstract

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 pass the transition zone (TZ) for ciliary retrieval, but how this passage is controlled remains elusive. Here, we show that phospholipase D (PLD)-laden BBSomes shed from retrograde IFT trains at the proximal ciliary region right above the TZ to act as Arf-like 3 (ARL3) GTPase-specific effectors in Chlamydomonas cilia. Under physiological condition, ARL3GDP binds to the membrane for diffusing into cilia. Following nucleotide exchange, ARL3GTP detaches from the ciliary membrane, binds to retrograde IFT train-shed and PLD-laden BBSomes at the proximal ciliary region right above the TZ, and recruits them to pass the TZ for ciliary retrieval likely via diffusion. ARL3 mediates the ciliary dynamics of certain signaling molecules through facilitating BBSome ciliary retrieval, providing a mechanistic understanding behind why ARL3-related Joubert syndrome shares overlapping phenotypes with Bardet-Biedl syndrome.

Funder

National Natural Science Foundation of China

China Postdoctoral Science Foundation

Publisher

Rockefeller University Press

Subject

Cell Biology

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