BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly

Seongjin Seo; Lisa M Baye; Nathan P Schulz; John S Beck; Qihong Zhang; Diane C Slusarski; Val C Sheffield

doi:10.1073/pnas.0910268107

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BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly

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BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly

Seongjin Seo, Lisa M Baye, Nathan P Schulz, John S Beck, Qihong Zhang, Diane C Slusarski and Val C Sheffield

Proceedings of the National Academy of Sciences - PNAS, Vol.107(4), pp.1488-1493

01/26/2010

DOI: 10.1073/pnas.0910268107

PMCID: PMC2824390

PMID: 20080638

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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.

Mutation

Cell Line

Bardet-Biedl Syndrome - enzymology

Centromere - enzymology

Group II Chaperonins - deficiency

Chaperonins - deficiency

Humans

Zebrafish - genetics

Mice, Knockout

Chaperonins - metabolism

Group II Chaperonins - genetics

Group II Chaperonins - metabolism

Animals

Chaperonin Containing TCP-1 - genetics

Zebrafish - metabolism

Protein Binding

Bardet-Biedl Syndrome - genetics

Mice

Chaperonin Containing TCP-1 - metabolism

Details

Title: Subtitle: BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly
Creators: Seongjin Seo - Department of Pediatrics, and Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA
Lisa M Baye
Nathan P Schulz
John S Beck
Qihong Zhang
Diane C Slusarski
Val C Sheffield
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.107(4), pp.1488-1493
DOI: 10.1073/pnas.0910268107
PMID: 20080638
PMCID: PMC2824390
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: United States
Grant note: T32 HL007121 / NHLBI NIH HHS Howard Hughes Medical Institute R01 EY017168 / NEI NIH HHS REY110298 / PHS HHS R01CA112369 / NCI NIH HHS REY017168 / PHS HHS R01 CA112369 / NCI NIH HHS
Language: English
Date published: 01/26/2010
Academic Unit: Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Biology; Ophthalmology and Visual Sciences
Record Identifier: 9983979954502771

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