title: CLIC5 stabilizes membrane-actin filament linkages at the base of hair cell stereocilia in a molecular complex with radixin, taperin, and myosin VI.
abstract: Chloride intracellular channel 5 protein (CLIC5) was originally isolated from microvilli in complex with actin binding proteins including ezrin, a member of the Ezrin-Radixin-Moesin (ERM) family of membrane-cytoskeletal linkers. CLIC5 concentrates at the base of hair cell stereocilia and is required for normal hearing and balance in mice, but its functional significance is poorly understood. This study investigated the role of CLIC5 in postnatal development and maintenance of hair bundles. Confocal and scanning electron microscopy of CLIC5-deficient jitterbug (jbg) mice revealed progressive fusion of stereocilia as early as postnatal day 10. Radixin (RDX), protein tyrosine phosphatase receptor Q (PTPRQ), and taperin (TPRN), deafness-associated proteins that also concentrate at the base of stereocilia, were mislocalized in fused stereocilia of jbg mice. TPRQ and RDX were dispersed even prior to stereocilia fusion. Biochemical assays showed interaction of CLIC5 with ERM proteins, TPRN, and possibly myosin VI (MYO6). In addition, CLIC5 and RDX failed to localize normally in fused stereocilia of MYO6 mutant mice. Based on these findings, we propose a model in which these proteins work together as a complex to stabilize linkages between the plasma membrane and subjacent actin cytoskeleton at the base of stereocilia.
authors.affiliation: Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland.
authors.forename: Felipe T
authors.initials: FT
authors.lastname: Salles
authors.forename: Leonardo R
authors.initials: LR
authors.lastname: Andrade
authors.forename: Soichi
authors.initials: S
authors.lastname: Tanda
authors.forename: M'hamed
authors.initials: M
authors.lastname: Grati
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Plona
authors.forename: Leona H
authors.initials: LH
authors.lastname: Gagnon
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Johnson
authors.forename: Bechara
authors.initials: B
authors.lastname: Kachar
authors.forename: Mark A
authors.initials: MA
authors.lastname: Berryman
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018995:Myosin Heavy Chains / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D059547:Stereocilia / Q000378:metabolism*
chemical_list: C514190:CLIC5 protein, mouse; D018118:Chloride Channels; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D011506:Proteins; C089785:myosin VI; C548552:taperin protein, mouse; C071776:radixin; D018995:Myosin Heavy Chains
keywords: PTPRQ; chloride intracellular channel 5 (CLIC5); cytoskeleton; deafness; ezrin-radixin-moesin (ERM); hair cell; myosin VI (MYO6); radixin; stereocilia; taperin