PUBLICATION
BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly
- Authors
- Seo, S., Baye, L.M., Schulz, N.P., Beck, J.S., Zhang, Q., Slusarski, D.C., and Sheffield, V.C.
- ID
- ZDB-PUB-100119-20
- Date
- 2010
- Source
- Proceedings of the National Academy of Sciences of the United States of America 107(4): 1488-1493 (Journal)
- Registered Authors
- Baye, Lisa, Slusarski, Diane C.
- Keywords
- Bardet-Biedl Syndrome, ciliopathy, molecular chaperone, protein trafficking
- MeSH Terms
-
- Animals
- Bardet-Biedl Syndrome/enzymology*
- Bardet-Biedl Syndrome/genetics
- Cell Line
- Centromere/enzymology
- Chaperonin Containing TCP-1/genetics
- Chaperonin Containing TCP-1/metabolism*
- Chaperonins/deficiency
- Chaperonins/metabolism
- Group II Chaperonins/deficiency
- Group II Chaperonins/genetics
- Group II Chaperonins/metabolism*
- Humans
- Mice
- Mice, Knockout
- Mutation
- Protein Binding
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 20080638 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Seo, S., Baye, L.M., Schulz, N.P., Beck, J.S., Zhang, Q., Slusarski, D.C., and Sheffield, V.C. (2010) BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly. Proceedings of the National Academy of Sciences of the United States of America. 107(4):1488-1493.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping