title: Ciliary proteins Bbs8 and Ift20 promote planar cell polarity in the cochlea.
abstract: Primary cilia have been implicated in the generation of planar cell polarity (PCP). However, variations in the severity of polarity defects in different cilia mutants, coupled with recent demonstrations of non-cilia-related actions of some cilia genes, make it difficult to determine the basis of these polarity defects. To address this issue, we evaluated PCP defects in cochlea from a selection of mice with mutations in cilia-related genes. Results indicated notable PCP defects, including mis-oriented hair cell stereociliary bundles, in Bbs8 and Ift20 single mutants that are more severe than in other cilia gene knockouts. In addition, deletion of either Bbs8 or Ift20 results in disruptions in asymmetric accumulation of the core PCP molecule Vangl2 in cochlear cells, suggesting a role for Bbs8 and/or Ift20, possibly upstream of core PCP asymmetry. Consistent with this, co-immunoprecipitation experiments indicate direct interactions of Bbs8 and Ift20 with Vangl2. We observed localization of Bbs and Ift proteins to filamentous actin as well as microtubules. This could implicate these molecules in selective trafficking of membrane proteins upstream of cytoskeletal reorganization, and identifies new roles for cilia-related proteins in cochlear PCP.
authors.affiliation: Section on Developmental Neuroscience, Laboratory of Cochlear Development, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA maysimerah@nei.nih.gov.
authors.forename: Helen L
authors.initials: HL
authors.lastname: May-Simera
authors.affiliation: Advanced Imaging Core, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Petralia
authors.affiliation: Planar Polarity and Plasticity Group, Institut National de la Santé et de la Recherche Médicale U862, Neurocenter Magendie, 33077 Bordeaux, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Montcouquiol
authors.affiliation: Advanced Imaging Core, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ya-Xian
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Section on Developmental Neuroscience, Laboratory of Cochlear Development, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Szarama
authors.affiliation: Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75235, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75235, USA.
authors.forename: Weichun
authors.initials: W
authors.lastname: Lin
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery and Department of Neurobiology & Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Deans
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Pazour
authors.affiliation: Section on Developmental Neuroscience, Laboratory of Cochlear Development, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Kelley
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology*; D002923:Cilia / Q000235:genetics* / Q000502:physiology / Q000648:ultrastructure; D003051:Cochlea / Q000196:embryology* / Q000648:ultrastructure; D003598:Cytoskeletal Proteins; D006198:Hair Cells, Auditory / Q000473:pathology; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C514104:Ift20 protein, mouse; C431577:Ltap protein, mouse; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C561225:Ttc8 protein, mouse
keywords: Actin; Cilia; Cochlea; Microtubules; Mouse; Polarity