title: Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle.
abstract: Deaf-blindness in three distinct genetic forms of Usher type I syndrome (USH1) is caused by defects in myosin VIIa, harmonin and cadherin 23. Despite being critical for hearing, the functions of these proteins in the inner ear remain elusive. Here we show that harmonin, a PDZ domain-containing protein, and cadherin 23 are both present in the growing stereocilia and that they bind to each other. Moreover, we demonstrate that harmonin b is an F-actin-bundling protein, which is thus likely to anchor cadherin 23 to the stereocilia microfilaments, thereby identifying a novel anchorage mode of the cadherins to the actin cytoskeleton. Moreover, harmonin b interacts directly with myosin VIIa, and is absent from the disorganized hair bundles of myosin VIIa mutant mice, suggesting that myosin VIIa conveys harmonin b along the actin core of the developing stereocilia. We propose that the shaping of the hair bundle relies on a functional unit composed of myosin VIIa, harmonin b and cadherin 23 that is essential to ensure the cohesion of the stereocilia.
authors.affiliation: Unité de Génétique des Déficits Sensoriels, CNRS URA 1968, 25 rue du Dr. Roux, 75724 Paris cedex 15, France.
authors.forename: Batiste
authors.initials: B
authors.lastname: Boëda
authors.forename: Aziz
authors.initials: A
authors.lastname: El-Amraoui
authors.forename: Amel
authors.initials: A
authors.lastname: Bahloul
authors.forename: Richard
authors.initials: R
authors.lastname: Goodyear
authors.forename: Laurent
authors.initials: L
authors.lastname: Daviet
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanchard
authors.forename: Isabelle
authors.initials: I
authors.lastname: Perfettini
authors.forename: Karl R
authors.initials: KR
authors.lastname: Fath
authors.forename: Spencer
authors.initials: S
authors.lastname: Shorte
authors.forename: Jan
authors.initials: J
authors.lastname: Reiners
authors.forename: Anne
authors.initials: A
authors.lastname: Houdusse
authors.forename: Pierre
authors.initials: P
authors.lastname: Legrain
authors.forename: Uwe
authors.initials: U
authors.lastname: Wolfrum
authors.forename: Guy
authors.initials: G
authors.lastname: Richardson
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000737:chemistry / Q000502:physiology*; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002460:Cell Line; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary / Q000378:metabolism; D004398:Dyneins; D015723:Gene Library; D006198:Hair Cells, Auditory / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D000081412:Myosin VIIa; D009218:Myosins / Q000737:chemistry / Q000502:physiology*; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C442480:CDH23 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D002352:Carrier Proteins; C499091:Cdh23 protein, mouse; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; C000631455:MYO7A protein, human; C000631456:Myo7a protein, mouse; C000631457:Myo7a protein, rat; D000081412:Myosin VIIa; D020033:Protein Isoforms; C118970:USH1C protein, human; C492262:Ush1c protein, mouse; C492261:Ush1c protein, rat; D009218:Myosins; D004398:Dyneins