Intraflagellar transport protein RABL5/IFT22 recruits the BBSome to the basal body through the GTPase ARL6/BBS3.

Autor:	Xue B; State Key Laboratory of Food Nutrition and Safety, Institute of Health Biotechnology, Tianjin University of Science and Technology, Tianjin, 30457, China., Liu YX; State Key Laboratory of Food Nutrition and Safety, Institute of Health Biotechnology, Tianjin University of Science and Technology, Tianjin, 30457, China., Dong B; State Key Laboratory of Food Nutrition and Safety, Institute of Health Biotechnology, Tianjin University of Science and Technology, Tianjin, 30457, China., Wingfield JL; Department of Cellular Biology, University of Georgia, Athens, GA 30602., Wu M; Department of Molecular and Cellular Physiology, Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208., Sun J; State Key Laboratory of Food Nutrition and Safety, Institute of Health Biotechnology, Tianjin University of Science and Technology, Tianjin, 30457, China., Lechtreck KF; Department of Cellular Biology, University of Georgia, Athens, GA 30602., Fan ZC; State Key Laboratory of Food Nutrition and Safety, Institute of Health Biotechnology, Tianjin University of Science and Technology, Tianjin, 30457, China; fanzhen@tust.edu.cn.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Feb 04; Vol. 117 (5), pp. 2496-2505. Date of Electronic Publication: 2020 Jan 17.
DOI:	10.1073/pnas.1901665117
Abstrakt:	Bardet-Biedl syndrome (BBS) is a ciliopathy caused by defects in the assembly or distribution of the BBSome, a conserved protein complex. The BBSome cycles via intraflagellar transport (IFT) through cilia to transport signaling proteins. How the BBSome is recruited to the basal body for binding to IFT trains for ciliary entry remains unknown. Here, we show that the Rab-like 5 GTPase IFT22 regulates basal body targeting of the BBSome in Chlamydomonas reinhardtii Our functional, biochemical and single particle in vivo imaging assays show that IFT22 is an active GTPase with low intrinsic GTPase activity. IFT22 is part of the IFT-B1 subcomplex but is not required for ciliary assembly. Independent of its association to IFT-B1, IFT22 binds and stabilizes the Arf-like 6 GTPase BBS3, a BBS protein that is not part of the BBSome. IFT22/BBS3 associates with the BBSome through an interaction between BBS3 and the BBSome. When both IFT22 and BBS3 are in their guanosine triphosphate (GTP)-bound states they recruit the BBSome to the basal body for coupling with the IFT-B1 subcomplex. The GTP-bound BBS3 likely remains to be associated with the BBSome upon ciliary entry. In contrast, IFT22 is not required for the transport of BBSomes in cilia, indicating that the BBSome is transferred from IFT22 to the IFT trains at the ciliary base. In summary, our data propose that nucleotide-dependent recruitment of the BBSome to the basal body by IFT22 regulates BBSome entry into cilia. Competing Interests: The authors declare no competing interest.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu