Bardet-Biedl Syndrome 3 protein promotes ciliary exit of the signaling protein phospholipase D via the BBSome
Abstract
Certain ciliary signaling proteins couple with the BBSome, a conserved complex of Bardet-Biedl syndrome (BBS) proteins, to load onto retrograde intraflagellar transport (IFT) trains for their removal out of cilia in Chlamydomonas reinhardtii. Here, we show that loss of the Arf-like 6 (ARL6) GTPase BBS3 causes the signaling protein phospholipase D (PLD) to accumulate in cilia. Upon targeting to the basal body, BBSomes enter and cycle through cilia via IFT, while BBS3 in a GTP-bound state separates from BBSomes, associates with the membrane, and translocates from the basal body to cilia by diffusion. Upon arriving at the ciliary tip, GTP-bound BBS3 binds and recruits BBSomes to the ciliary membrane for interacting with PLD, thus making the PLD-laden BBSomes available to load onto retrograde IFT trains for ciliary exit. Therefore, BBS3 promotes PLD exit from cilia via the BBSome providing a regulatory mechanism for ciliary signaling protein removal out of cilia.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
International Center for Genetic Engineering and Biotechnology (CRP/CHN15-01)
- Zhen-Chuan Fan
National Natural Science Foundation of China (41876134)
- Jun Sun
National Institutes of Health (GM110413)
- Karl F Lechtreck
National Natural Science Foundation of China (32070698)
- Zhen-Chuan Fan
Tianjin Municipal Science and Technology Bureau (19PTSYJC00050)
- Zhen-Chuan Fan
Tianjin Municipal Science and Technology Bureau (18JCZDJC34100)
- Zhen-Chuan Fan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Junmin Pan, Tsinghua University, China
Publication history
- Received: May 20, 2020
- Accepted: February 13, 2021
- Accepted Manuscript published: February 15, 2021 (version 1)
- Version of Record published: March 16, 2021 (version 2)
Copyright
© 2021, Liu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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