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| Subject Categories: Cell & Tissue Architecture | Molecular Biology of Disease |
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| The EMBO Journal
(2002) 21, 6689–6699, doi: 10.1093/emboj/cdf689 |
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| Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle |
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| Batiste Boëda1, 8, Aziz El-Amraoui1, 8, Amel Bahloul2, Richard Goodyear3, Laurent Daviet4, Stéphane Blanchard1, Isabelle Perfettini1, Karl R. Fath5, 6, Spencer Shorte7, Jan Reiners5, Anne Houdusse2, Pierre Legrain4, Uwe Wolfrum5, Guy Richardson3 and Christine Petit1 |
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1 Unité de Génétique des Déficits Sensoriels, CNRS URA 1968, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France 2 UMR 144 CNRS/IC, Institut Curie, 26 rue d'Ulm, 75248 Paris cedex 05, France 3 School of Biological Sciences, The University of Sussex, Falmer, Brighton BN1 9QG, UK 4 Hybrigenics, 3−5 impasse Reille, 75014 Paris, France 5 Institut für Zoologie, Johannes Gutenberg-Universität Mainz, D-55099 Mainz, Germany 6 Present address: Queens College of CUNY, 65−30 Kissena Blvd, Flushing, NY 11367, USA 7 Centre d'Imagerie Dynamique, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France 8 B.Boëda and A.El-Amraoui contributed equally to this work To whom correspondence should be addressed Christine Petit, cpetit@pasteur.fr Received 19 August 2002; Revised 30 October 2002; Accepted 30 October 2002. |
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| Abstract |
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| 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. |
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| Keywords: cadherin 23, hair bundle, harmonin, myosin VIIa, Usher syndrome |
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