BBS7 is required for BBSome formation and its absence in mice results in Bardet-Biedl syndrome phenotypes and selective abnormalities in membrane protein trafficking

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

doi:10.1242/jcs.111740

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BBS7 is required for BBSome formation and its absence in mice results in Bardet-Biedl syndrome phenotypes and selective abnormalities in membrane protein trafficking

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BBS7 is required for BBSome formation and its absence in mice results in Bardet-Biedl syndrome phenotypes and selective abnormalities in membrane protein trafficking

Qihong Zhang, Darryl Nishimura, Tim Vogel, Jianqiang Shao, Ruth Swiderski, Terry Yin, Charles Searby, Calvin S Carter, Gunhee Kim, Kevin Bugge, …

Journal of cell science, Vol.126(Pt 11), pp.2372-2380

06/01/2013

DOI: 10.1242/jcs.111740

PMCID: PMC3679484

PMID: 23572516

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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.

Molecular Chaperones - metabolism

Bardet-Biedl Syndrome - metabolism

Male

Multiprotein Complexes - genetics

Cell Membrane - genetics

Obesity - genetics

Retinal Degeneration - metabolism

Receptors, Dopamine D1 - metabolism

Multiprotein Complexes - metabolism

Infertility, Male - genetics

Bardet-Biedl Syndrome - pathology

Cell Membrane - pathology

Bardet-Biedl Syndrome - genetics

Cell Membrane - metabolism

Disease Models, Animal

TRPP Cation Channels - metabolism

Cilia - pathology

Retinal Degeneration - genetics

Molecular Chaperones - genetics

Infertility, Male - pathology

Cilia - metabolism

TRPP Cation Channels - genetics

Cilia - genetics

Mice, Knockout

Obesity - metabolism

Obesity - pathology

Carrier Proteins - genetics

Animals

Carrier Proteins - metabolism

Infertility, Male - metabolism

Mice

Retinal Degeneration - pathology

Receptors, Dopamine D1 - genetics

Details

Title: Subtitle: BBS7 is required for BBSome formation and its absence in mice results in Bardet-Biedl syndrome phenotypes and selective abnormalities in membrane protein trafficking
Creators: Qihong Zhang - Department of Pediatrics, Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA
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
Resource Type: Journal article
Publication Details: Journal of cell science, Vol.126(Pt 11), pp.2372-2380
DOI: 10.1242/jcs.111740
PMID: 23572516
PMCID: PMC3679484
NLM abbreviation: J Cell Sci
ISSN: 0021-9533
eISSN: 1477-9137
Publisher: England
Grant note: EY110298 / NEI NIH HHS R01 EY011298 / NEI NIH HHS R01 NS083543 / NINDS NIH HHS Howard Hughes Medical Institute EY01768 / NEI NIH HHS R01 EY017168 / NEI NIH HHS
Language: English
Date published: 06/01/2013
Academic Unit: Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983980094302771

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