title: XIRP2, an actin-binding protein essential for inner ear hair-cell stereocilia.
abstract: Hair cells of the inner ear are mechanoreceptors for hearing and balance, and proteins highly enriched in hair cells may have specific roles in the development and maintenance of the mechanotransduction apparatus. We identified XIRP2/mXinβ as an enriched protein likely to be essential for hair cells. We found that different isoforms of this protein are expressed and differentially located: short splice forms (also called XEPLIN) are targeted more to stereocilia, whereas two long isoforms containing a XIN-repeat domain are in both stereocilia and cuticular plates. Mice lacking the Xirp2 gene developed normal stereocilia bundles, but these degenerated with time: stereocilia were lost and long membranous protrusions emanated from the nearby apical surfaces. At an ultrastructural level, the paracrystalline actin filaments became disorganized. XIRP2 is apparently involved in the maintenance of actin structures in stereocilia and cuticular plates of hair cells, and perhaps in other organs where it is expressed.
authors.affiliation: Howard Hughes Medical Institute and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; Department of Otology and Laryngology, Massachusetts Eye and Ear and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Déborah I
authors.initials: DI
authors.lastname: Scheffer
authors.affiliation: Howard Hughes Medical Institute and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Duan-Sun
authors.initials: DS
authors.lastname: Zhang
authors.affiliation: Howard Hughes Medical Institute and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Shen
authors.affiliation: Howard Hughes Medical Institute and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Artur
authors.initials: A
authors.lastname: Indzhykulian
authors.affiliation: Howard Hughes Medical Institute and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: K Domenica
authors.initials: KD
authors.lastname: Karavitaki
authors.affiliation: Image and Data Analysis Core, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yichao Joy
authors.initials: YJ
authors.lastname: Xu
authors.affiliation: Department of Biology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Qinchuan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Biology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Jim Jung-Ching
authors.initials: JJ
authors.lastname: Lin
authors.affiliation: Department of Otology and Laryngology, Massachusetts Eye and Ear and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Zheng-Yi
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Howard Hughes Medical Institute and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: dcorey@hms.harvard.edu.
authors.forename: David P
authors.initials: DP
authors.lastname: Corey
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006198:Hair Cells, Auditory / Q000378:metabolism* / Q000648:ultrastructure; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D059547:Stereocilia / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C500305:XIRP2 protein, mouse