Bardet-Biedl Syndrome 3 protein promotes ciliary exit of the signaling protein phospholipase D via the BBSome
- Tianjin University of Science and Technology, China
- University of Georgia, United States
- Albany Medical College, United States
- China Agricultural University, China
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.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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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.
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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Bardet-Biedl Syndrome 3 protein promotes ciliary exit of the signaling protein phospholipase D via the BBSome
eLife 10:e59119.
https://doi.org/10.7554/eLife.59119
