Molecular Characterization of the Ankle-Link Complex in Cochlear Hair Cells and Its Role in the Hair Bundle Functioning
| Autor: | Pascal Martin, Nicolas Michalski, Dominique Weil, Amel Bahloul, Gaelle M. Lefèvre, Hideshi Yagi, Jean-Pierre Hardelin, Jérémie Barral, Vincent Michel, Makoto Sato, Sébastien Chardenoux, Christine Petit |
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| Přispěvatelé: | Génétique des Déficits Sensoriels, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Physico-Chimie Curie [Institut Curie] (PCC), Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2007 |
| Předmět: |
Cell type
Patch-Clamp Techniques Stereocilia (inner ear) PDZ domain Biology Mechanotransduction Cellular Membrane Potentials Receptors G-Protein-Coupled Adenylyl cyclase Mice chemistry.chemical_compound Organ Culture Techniques Hair Cells Auditory adenylyl cyclase 6 otorhinolaryngologic diseases Animals Cilia Egtazic Acid Cochlea Chelating Agents Mice Knockout Extracellular Matrix Proteins Cadherin General Neuroscience hair bundle Subtilisin ankle link Gene Expression Regulation Developmental Membrane Proteins Articles Anatomy Embryo Mammalian Transmembrane protein Cell biology Animals Newborn chemistry Microscopy Electron Scanning [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] sense organs Vlgr1 Carrier Proteins Usher syndrome Transduction (physiology) Adenylyl Cyclases |
| Zdroj: | Journal of Neuroscience Journal of Neuroscience, 2007, 27 (24), pp.6478-6488. ⟨10.1523/JNEUROSCI.0342-07.2007⟩ |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.0342-07.2007 |
| Popis: | International audience; Several lines of evidence indicate that very large G-protein-coupled receptor 1 (Vlgr1) makes up the ankle links that connect the stereocilia of hair cells at their base. Here, we show that the transmembrane protein usherin, the putative transmembrane protein vezatin, and the PDZ (postsynaptic density-95/Discs large/zona occludens-1) domain-containing submembrane protein whirlin are colocalized with Vlgr1 at the stereocilia base in developing cochlear hair cells and are absent in Vlgr1 Ϫ/Ϫ mice that lack the ankle links. Direct in vitro interactions between these four proteins further support their involvement in a molecular complex associated with the ankle links and scaffolded by whirlin. In addition, the delocalization of these proteins in myosin VIIa defective mutant mice as well as the myosin VIIa tail direct interactions with vezatin, whirlin, and, we show, Vlgr1 and usherin, suggest that myosin VIIa conveys proteins of the ankle-link complex to the stereocilia. Adenylyl cyclase 6, which was found at the base of stereocilia, was both overexpressed and mislocated in Vlgr1 Ϫ/Ϫ mice. In postnatal day 7 Vlgr1 Ϫ/Ϫ mice, mechanoelectrical transduction currents evoked by displacements of the hair bundle toward the tallest stereocilia (i.e., in the excitatory direction) were reduced in outer but not inner hair cells. In both cell types, stimulation of the hair bundle in the opposite direction paradoxically resulted in significant transduction currents. The absence of ankle-linkmediated cohesive forces within hair bundles lacking Vlgr1 may account for the electrophysiological results. However, because some long cadherin-23 isoforms could no longer be detected in Vlgr1 Ϫ/Ϫ mice shortly after birth, the loss of some apical links could be involved too. The premature disappearance of these cadherin isoforms in the Vlgr1 Ϫ/Ϫ mutant argues in favor of a signaling function of the ankle links in hair bundle differentiation. |
| Databáze: | OpenAIRE |
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