The conserved Bardet-Biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia.
The BBSome is a complex of Bardet-Biedl Syndrome (BBS) proteins that shares common structural elements with COPI, COPII, and clathrin coats. Here, we show that the BBSome constitutes a coat complex that sorts membrane proteins to primary cilia. The BBSome is the major effector of the Arf-like GTPase Arl6/BBS3, and the BBSome and GTP-bound Arl6 colocalize at ciliary punctae in an interdependent manner. Strikingly, Arl6(GTP)-mediated recruitment of the BBSome to synthetic liposomes produces distinct patches of polymerized coat apposed onto the lipid bilayer. Finally, the ciliary targeting signal of somatostatin receptor 3 needs to be directly recognized by the BBSome in order to mediate targeting of membrane proteins to cilia. Thus, we propose that trafficking of BBSome cargoes to cilia entails the coupling of BBSome coat polymerization to the recognition of sorting signals by the BBSome.
Jin
Hua
H
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305-5345, USA.
White
Susan Roehl
SR
Shida
Toshinobu
T
Schulz
Stefan
S
Aguiar
Mike
M
Gygi
Steven P
SP
Bazan
J Fernando
JF
Nachury
Maxence V
MV
D020727:ADP-Ribosylation Factors / Q000378:metabolism; D000818:Animals; D020788:Bardet-Biedl Syndrome / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002923:Cilia / Q000378:metabolism*; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D017510:Protein Folding; D021381:Protein Transport; D017481:Receptors, Somatostatin / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D014020:Tissue Extracts / Q000378:metabolism
D008081:Liposomes; D046912:Multiprotein Complexes; D010743:Phospholipids; D017481:Receptors, Somatostatin; D014020:Tissue Extracts; C103631:somatostatin receptor 3; C491435:ARL6 protein, human; D020727:ADP-Ribosylation Factors; C122027:Arl6 protein, mouse