BBS6, BBS10, and BBS12 Form a Complex with CCT/TRiC Family Chaperonins and Mediate BBSome Assembly

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2010 Jan 19

PMID 20080638

Citations 174

Authors

Seongjin Seo

Lisa M Baye

Nathan P Schulz

John S Beck

Qihong Zhang

Diane C Slusarski

Val C Sheffield

Affiliations

Soon will be listed here.

Abstract

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.

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