title: BBS7 is required for BBSome formation and its absence in mice results in Bardet-Biedl syndrome phenotypes and selective abnormalities in membrane protein trafficking.
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.
authors.affiliation: Department of Pediatrics, Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Qihong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Darryl
authors.initials: D
authors.lastname: Nishimura
authors.forename: Tim
authors.initials: T
authors.lastname: Vogel
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Shao
authors.forename: Ruth
authors.initials: R
authors.lastname: Swiderski
authors.forename: Terry
authors.initials: T
authors.lastname: Yin
authors.forename: Charles
authors.initials: C
authors.lastname: Searby
authors.forename: Calvin S
authors.initials: CS
authors.lastname: Carter
authors.forename: Gunhee
authors.initials: G
authors.lastname: Kim
authors.forename: Kevin
authors.initials: K
authors.lastname: Bugge
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D020788:Bardet-Biedl Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002923:Cilia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins; D004195:Disease Models, Animal; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050396:TRPP Cation Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; D017447:Receptors, Dopamine D1; D050396:TRPP Cation Channels; C584290:BBS7 protein, mouse
keywords: BBSome; Bardet Biedl syndrome; Cilia; Protein trafficking