title: Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport.
abstract: Bardet-Biedl syndrome (BBS) is a genetically heterogeneous developmental disorder whose molecular basis is largely unknown. Here, we show that mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia. C. elegans BBS proteins localize predominantly at the base of cilia, and like proteins involved in intraflagellar transport (IFT), a process necessary for cilia biogenesis and maintenance, move bidirectionally along the ciliary axoneme. Importantly, we demonstrate that BBS-7 and BBS-8 are required for the normal localization/motility of the IFT proteins OSM-5/Polaris and CHE-11, and to a notably lesser extent, CHE-2. We propose that BBS proteins play important, selective roles in the assembly and/or function of IFT particle components. Our findings also suggest that some of the cardinal and secondary symptoms of BBS, such as obesity, diabetes, cardiomyopathy, and learning defects may result from cilia dysfunction.
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, B.C. V5A 1S6, Canada.
authors.forename: Oliver E
authors.initials: OE
authors.lastname: Blacque
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Reardon
authors.forename: Chunmei
authors.initials: C
authors.lastname: Li
authors.forename: Jonathan
authors.initials: J
authors.lastname: McCarthy
authors.forename: Moe R
authors.initials: MR
authors.lastname: Mahjoub
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ansley
authors.forename: Jose L
authors.initials: JL
authors.lastname: Badano
authors.forename: Allan K
authors.initials: AK
authors.lastname: Mah
authors.forename: Philip L
authors.initials: PL
authors.lastname: Beales
authors.forename: William S
authors.initials: WS
authors.lastname: Davidson
authors.forename: Robert C
authors.initials: RC
authors.lastname: Johnsen
authors.forename: Mark
authors.initials: M
authors.lastname: Audeh
authors.forename: Ronald H A
authors.initials: RH
authors.lastname: Plasterk
authors.forename: David L
authors.initials: DL
authors.lastname: Baillie
authors.forename: Nicholas
authors.initials: N
authors.lastname: Katsanis
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Quarmby
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wicks
authors.forename: Michel R
authors.initials: MR
authors.lastname: Leroux
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis / Q000235:genetics; D002923:Cilia / Q000473:pathology* / Q000648:ultrastructure; D003598:Cytoskeletal Proteins; D005407:Flagella / Q000378:metabolism*; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D011506:Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C473308:Bbs7 protein, human; D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; D015801:Helminth Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; C400683:che-2 protein, C elegans; C427364:osm-5 protein, C elegans