BBS7 is Required for BBSome Formation and Its Absence in Mice Results in Bardet-Biedl Syndrome Phenotypes and Selective Abnormalities in Membrane Protein Trafficking

Overview

Journal J Cell Sci

Specialty Cell Biology

Date 2013 Apr 11

PMID 23572516

Citations 83

Authors

Qihong Zhang

Darryl Nishimura

Tim Vogel

Jianqiang Shao

Ruth Swiderski

Terry Yin

Charles Searby

Calvin S Carter

Gunhee Kim

Kevin Bugge

Edwin M Stone

Val C Sheffield

Affiliations

Soon will be listed here.

Abstract

Bardet-Biedl Syndrome (BBS) is a pleiotropic and genetically heterozygous disorder caused independently by numerous genes (BBS1-BBS17). Seven highly conserved BBS proteins (BBS1, 2, 4, 5, 7, 8 and 9) form a complex known as the BBSome, which functions in ciliary membrane biogenesis. BBS7 is both a unique subunit of the BBSome and displays direct physical interaction with a second BBS complex, the BBS chaperonin complex. To examine the in vivo function of BBS7, we generated Bbs7 knockout mice. Bbs7(-/-) mice show similar phenotypes to other BBS gene mutant mice including retinal degeneration, obesity, ventriculomegaly and male infertility characterized by abnormal spermatozoa flagellar axonemes. Using tissues from Bbs7(-/-) mice, we show that BBS7 is required for BBSome formation, and that BBS7 and BBS2 depend on each other for protein stability. Although the BBSome serves as a coat complex for ciliary membrane proteins, BBS7 is not required for the localization of ciliary membrane proteins polycystin-1, polycystin-2, or bitter taste receptors, but absence of BBS7 leads to abnormal accumulation of the dopamine D1 receptor to the ciliary membrane, indicating that BBS7 is involved in specific membrane protein localization to cilia.

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