Harmonin-b, an actin-binding scaffold protein, is involved in the adaptation of mechanoelectrical transduction by sensory hair cells
| Autor: | Elisa Caberlotto, Jean-Yves Tinevez, Christine Petit, Christophe Houbron, Guy P. Richardson, Emilie Bizard, Pascal Martin, Vincent Michel, Nicolas Michalski, Alexander F. J. van Aken, Gaelle M. Lefèvre, Jean-Pierre Hardelin, Corné J. Kros, Dominique Weil |
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| Přispěvatelé: | Chaire Génétique et physiologie cellulaire, Collège de France (CdF (institution)), Génétique des Déficits Sensoriels, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), School of Life Sciences, University of Sussex, Physico-Chimie-Curie (PCC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC), Imagopole (CITECH), Institut Pasteur [Paris], Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), N.M. was supported by a fellowship from the Fondation pour la Recherche Médicale and the Ministère de l'Education Nationale, de la Recherche et de la Technologie. This work was supported by the Fondation Raymonde et Guy Strittmatter, the European Commission FP6 Integrated Project EuroHear LSHG-CT-2004-512063, Ernst-Jung Stiftung für Medizin Preis, FAUN Stiftung (Suchert Foundation) and the Ministère de la Recherche-ACI Interface Physique-Chimie-Biologie-DRAB02/102., We thank Jacqueline Levilliers for her help in the preparation of the manuscript and Jacques Boutet de Monvel for critical reading of the manuscript., Collège de France - Chaire Génétique et physiologie cellulaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Tinevez, Jean-Yves |
| Rok vydání: | 2009 |
| Předmět: |
Scaffold protein
Patch-Clamp Techniques MESH: Cytoskeletal Proteins MESH: Mice Mutant Strains Physiology [SDV]Life Sciences [q-bio] Stereocilia (inner ear) Clinical Biochemistry MESH: Adaptation Physiological Action Potentials Fluorescent Antibody Technique Cell Cycle Proteins MESH: Mechanotransduction Cellular / physiology Mechanotransduction Cellular Mice MESH: Hair Cells Auditory Inner / metabolism 0302 clinical medicine MESH: Animals MESH: Fluorescent Antibody Technique Mechanoelectrical transduction 0303 health sciences Anatomy Hair bundle Adaptation Physiological Cochlea [SDV] Life Sciences [q-bio] medicine.anatomical_structure MESH: Carrier Proteins / metabolism [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Hair cell Transduction (physiology) Vestibule Vestibular system MESH: Microscopy Electron Scanning PDZ domain Biology 03 medical and health sciences MESH: Action Potentials / physiology Physiology (medical) MESH: Patch-Clamp Techniques otorhinolaryngologic diseases medicine Animals Inner ear [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Adaptation MESH: Mice Harmonin 030304 developmental biology Hair Cells Auditory Inner Mice Mutant Strains Cytoskeletal Proteins Microscopy Electron Scanning Biophysics sense organs Carrier Proteins Tip link 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | Pflügers Archiv European Journal of Physiology Pflügers Archiv European Journal of Physiology, Springer Verlag, 2009, 459 (1), pp.115-130. ⟨10.1007/s00424-009-0711-x⟩ Pflügers Archiv European Journal of Physiology, 2009, 459 (1), pp.115-130. ⟨10.1007/s00424-009-0711-x⟩ Pflugers Archiv |
| ISSN: | 1432-2013 0031-6768 |
| Popis: | We assessed the involvement of harmonin-b, a submembranous protein containing PDZ domains, in the mechanoelectrical transduction machinery of inner ear hair cells. Harmonin-b is located in the region of the upper insertion point of the tip link that joins adjacent stereocilia from different rows and that is believed to gate transducer channel(s) located in the region of the tip link's lower insertion point. In Ush1cdfcr-2J/dfcr-2J mutant mice defective for harmonin-b, step deflections of the hair bundle evoked transduction currents with altered speed and extent of adaptation. In utricular hair cells, hair bundle morphology and maximal transduction currents were similar to those observed in wild-type mice, but adaptation was faster and more complete. Cochlear outer hair cells displayed reduced maximal transduction currents, which may be the consequence of moderate structural anomalies of their hair bundles. Their adaptation was slower and displayed a variable extent. The latter was positively correlated with the magnitude of the maximal transduction current, but the cells that showed the largest currents could be either hyperadaptive or hypoadaptive. To interpret our observations, we used a theoretical description of mechanoelectrical transduction based on the gating spring theory and a motor model of adaptation. Simulations could account for the characteristics of transduction currents in wild-type and mutant hair cells, both vestibular and cochlear. They led us to conclude that harmonin-b operates as an intracellular link that limits adaptation and engages adaptation motors, a dual role consistent with the scaffolding property of the protein and its binding to both actin filaments and the tip link component cadherin-23. Electronic supplementary material The online version of this article (doi:10.1007/s00424-009-0711-x) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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