Interaction of protocadherin-15 with the scaffold protein whirlin supports its anchoring of hair-bundle lateral links in cochlear hair cells
| Autor: | Elise Pepermans, Vincent Michel, Alain Aghaie, Jean-Pierre Hardelin, Amel Bahloul, Sylvie Nouaille, Isabelle Perfettini, Patrick England, Christine Petit, Jacques Boutet de Monvel, Florent Delhommel, Nicolas Wolff |
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| Přispěvatelé: | Génétique et Physiologie de l'Audition, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), ED 515 - Complexité du vivant, Sorbonne Université (SU), Institut de l'Audition [Paris] (IDA), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Biophysique Moléculaire (plateforme) - Molecular Biophysics (platform), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Structural Biology (Neuherberg), Helmholtz-Zentrum München (HZM), Récepteurs Canaux - Channel Receptors, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Chaire Génétique et physiologie cellulaire, Collège de France (CdF (institution)), Stanford University, This work was supported by Institut Pasteur PTR program No.483, by Agence Nationale de la Recherche (ANR) within the framework of the Investissements d'Avenir program (ANR‐15‐RHUS‐0001), Laboratoire d'excellence (LabEx) Lifesenses (ANR‐10‐LABX‐65), ANR‐11‐IDEX‐0004‐02, ANR‐11‐BSV5‐0011, and grants from Fondation Agir pour l'Audition, the BNP Paribas Foundation, the FAUN Stiftung, the LHW‐Stiftung and Mrs. Errera Hoechstetter., ANR-15-RHUS-0001,LIGHT4DEAF,ECLAIRER LA SURDITÉ : UNE APPROCHE HOLISTIQUE DU SYNDROME D'USHER(2015), ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), ANR-11-BSV5-0011,EARMEC,Propriétés mécaniques, actives et passives, de la touffe ciliaire des cellules mécano-sensorielles ciliées le long de l'axe tonotopique de la cochlée des mammifères.(2011), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Helmholtz Zentrum München = German Research Center for Environmental Health, Collège de France - Chaire Génétique et physiologie cellulaire, Gestionnaire, HAL Sorbonne Université 5, ECLAIRER LA SURDITÉ : UNE APPROCHE HOLISTIQUE DU SYNDROME D'USHER - - LIGHT4DEAF2015 - ANR-15-RHUS-0001 - RHUS - VALID, Sorbonne Universités à Paris pour l'Enseignement et la Recherche - - SUPER2011 - ANR-11-IDEX-0004 - IDEX - VALID, BLANC - Propriétés mécaniques, actives et passives, de la touffe ciliaire des cellules mécano-sensorielles ciliées le long de l'axe tonotopique de la cochlée des mammifères. - - EARMEC2011 - ANR-11-BSV5-0011 - BLANC - VALID |
| Rok vydání: | 2019 |
| Předmět: |
Scaffold protein
Male Stereocilia (inner ear) PDZ domain lcsh:Medicine Cadherin Related Proteins Diseases [SDV.GEN] Life Sciences [q-bio]/Genetics Mechanotransduction Cellular Biochemistry Article Stereocilia 03 medical and health sciences Mice 0302 clinical medicine CDH23 Hair Cells Auditory medicine otorhinolaryngologic diseases Animals Protein Isoforms Protein Precursors Cytoskeleton lcsh:Science 030304 developmental biology 0303 health sciences [SDV.GEN]Life Sciences [q-bio]/Genetics Multidisciplinary Chemistry lcsh:R Membrane Proteins Cell Differentiation Actin cytoskeleton Cadherins Cell biology Cochlea Mice Inbred C57BL medicine.anatomical_structure Microscopy Electron Scanning lcsh:Q Female Hair cell sense organs Engineering sciences. Technology 030217 neurology & neurosurgery PCDH15 Neuroscience |
| Zdroj: | Scientific Reports Scientific reports Scientific Reports, Nature Publishing Group, 2020, 10 (1), pp.16430. ⟨10.1038/s41598-020-73158-1⟩ Scientific Reports, 2020, 10 (1), pp.16430. ⟨10.1038/s41598-020-73158-1⟩ Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020) |
| ISSN: | 2045-2322 |
| Popis: | International audience; The hair bundle of cochlear hair cells is the site of auditory mechanoelectrical transduction. It is formed by three rows of stiff microvilli-like protrusions of graduated heights, the short, middle-sized, and tall stereocilia. In developing and mature sensory hair cells, stereocilia are connected to each other by various types of fibrous links. Two unconventional cadherins, protocadherin-15 (PCDH15) and cadherin-23 (CDH23), form the tip-links, whose tension gates the hair cell mechanoelectrical transduction channels. These proteins also form transient lateral links connecting neighboring stereocilia during hair bundle morphogenesis. The proteins involved in anchoring these diverse links to the stereocilia dense actin cytoskeleton remain largely unknown. We show that the long isoform of whirlin (L-whirlin), a PDZ domain-containing submembrane scaffold protein, is present at the tips of the tall stereocilia in mature hair cells, together with PCDH15 isoforms CD1 and CD2; L-whirlin localization to the ankle-link region in developing hair bundles moreover depends on the presence of PCDH15-CD1 also localizing there. We further demonstrate that L-whirlin binds to PCDH15 and CDH23 with moderate-to-high affinities in vitro. From these results, we suggest that L-whirlin is part of the molecular complexes bridging PCDH15-, and possibly CDH23-containing lateral links to the cytoskeleton in immature and mature stereocilia. The sensory cells of the cochlea (inner and outer hair cells) convert acoustic waves into receptor potentials by the process of mechanoelectrical transduction (MET) 1,2. This process takes place in the hair bundle, a mechanosensi-tive antenna formed by thick and stiff microvilli-like protrusions called stereocilia, organized in three rows of graduated height (i.e., short, middle-sized, and tall stereocilia) at the apical surface of the hair cells. Stereocilia are connected, within and between rows, by various types of fibrous links, expressed both in the developing and the mature cochlea. According to the current view of the MET process, cationic transducer channels located at the tips of short and middle-sized stereocilia 3 are gated by the sound-evoked periodic tension of the tip link, an open |
| Databáze: | OpenAIRE |
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