title: Myosin-XVa is required for tip localization of whirlin and differential elongation of hair-cell stereocilia.
abstract: Stereocilia are microvilli-derived mechanosensory organelles that are arranged in rows of graded heights on the apical surface of inner-ear hair cells. The 'staircase'-like architecture of stereocilia bundles is necessary to detect sound and head movement, and is achieved through differential elongation of the actin core of each stereocilium to a predetermined length. Abnormally short stereocilia bundles that have a diminished staircase are characteristic of the shaker 2 (Myo15a(sh2)) and whirler (Whrn(wi)) strains of deaf mice. We show that myosin-XVa is a motor protein that, in vivo, interacts with the third PDZ domain of whirlin through its carboxy-terminal PDZ-ligand. Myosin-XVa then delivers whirlin to the tips of stereocilia. Moreover, if green fluorescent protein (GFP)-Myo15a is transfected into hair cells of Myo15a(sh2) mice, the wild-type pattern of hair bundles is restored by recruitment of endogenous whirlin to the tips of stereocilia. The interaction of myosin-XVa and whirlin is therefore a key event in hair-bundle morphogenesis.
authors.affiliation: Section on Human Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
authors.forename: Inna A
authors.initials: IA
authors.lastname: Belyantseva
authors.forename: Erich T
authors.initials: ET
authors.lastname: Boger
authors.forename: Sadaf
authors.initials: S
authors.lastname: Naz
authors.forename: Gregory I
authors.initials: GI
authors.lastname: Frolenkov
authors.forename: James R
authors.initials: JR
authors.lastname: Sellers
authors.forename: Zubair M
authors.initials: ZM
authors.lastname: Ahmed
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Griffith
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Friedman
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D002923:Cilia / Q000648:ultrastructure*; D003638:Deafness / Q000235:genetics*; D049452:Green Fluorescent Proteins; D006199:Hair Cells, Auditory, Inner / Q000254:growth & development* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000378:metabolism; D009218:Myosins / Q000502:physiology*
chemical_list: D000199:Actins; D008565:Membrane Proteins; D020409:Molecular Motor Proteins; C114013:Myo15 protein, mouse; C477218:Whrn protein, mouse; D049452:Green Fluorescent Proteins; D009218:Myosins