BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly.
Bardet-Biedl syndrome (BBS) is a human genetic disorder resulting in obesity, retinal degeneration, polydactyly, and nephropathy. Recent studies indicate that trafficking defects to the ciliary membrane are involved in this syndrome. Here, we show that a novel complex composed of three chaperonin-like BBS proteins (BBS6, BBS10, and BBS12) and CCT/TRiC family chaperonins mediates BBSome assembly, which transports vesicles to the cilia. Chaperonin-like BBS proteins interact with a subset of BBSome subunits and promote their association with CCT chaperonins. CCT activity is essential for BBSome assembly, and knockdown of CCT chaperonins in zebrafish results in BBS phenotypes. Many disease-causing mutations found in BBS6, BBS10, and BBS12 disrupt interactions among these BBS proteins. Our data demonstrate that BBS6, BBS10, and BBS12 are necessary for BBSome assembly, and that impaired BBSome assembly contributes to the etiology of BBS phenotypes associated with the loss of function of these three BBS genes.
Seo
Seongjin
S
Department of Pediatrics, and Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA.
Baye
Lisa M
LM
Schulz
Nathan P
NP
Beck
John S
JS
Zhang
Qihong
Q
Slusarski
Diane C
DC
Sheffield
Val C
VC
D000818:Animals; D020788:Bardet-Biedl Syndrome / Q000201:enzymology* / Q000235:genetics; D002460:Cell Line; D002503:Centromere / Q000201:enzymology; D056404:Chaperonin Containing TCP-1 / Q000235:genetics / Q000378:metabolism*; D018833:Chaperonins / Q000172:deficiency / Q000378:metabolism; D056385:Group II Chaperonins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D011485:Protein Binding; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism
C512111:BBS10 protein, human; C547663:BBS10 protein, mouse; C517002:BBS12 protein, human; C547664:Bbs12 protein, mouse; C414726:MKKS protein, human; C506279:Mkks protein, mouse; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins; D056385:Group II Chaperonins