title: The tip-link molecular complex of the auditory mechano-electrical transduction machinery.
abstract: Sound waves are converted into electrical signals by a process of mechano-electrical transduction (MET), which takes place in the hair bundle of cochlear hair cells. In response to the mechanical stimulus of the hair bundle, the tip-links, key components of the MET machinery, are tensioned and the MET channels open, which results in the generation of the cell receptor potential. Tip-links are composed of cadherin-23 (Cdh23) and protocadherin-15 (Pcdh15), both non-conventional cadherins, that form the upper and the lower part of these links, respectively. Here, we review the various Pcdh15 isoforms present in the organ of Corti, their localization in the auditory hair bundles, their involvement in the molecular complex forming the tip-link, and their interactions with transmembrane molecules that are components of the lower MET machinery.
authors.affiliation: Institut Pasteur, Unité de Génétique et Physiologie de l'Audition, 75724 Paris, Cedex 15, France; INSERM UMRS 1120 (Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche en Santé), 75015 Paris, France; Université Pierre et Marie Curie (Paris VI), 75005 Paris, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Pepermans
authors.affiliation: Institut Pasteur, Unité de Génétique et Physiologie de l'Audition, 75724 Paris, Cedex 15, France; INSERM UMRS 1120 (Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche en Santé), 75015 Paris, France; Université Pierre et Marie Curie (Paris VI), 75005 Paris, France; Collège de France, 75231 Paris, Cedex 05, France. Electronic address: cpetit@pasteur.fr.
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000737:chemistry / Q000502:physiology*; D006198:Hair Cells, Auditory / Q000378:metabolism*; D006309:Hearing / Q000502:physiology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009925:Organ of Corti / Q000378:metabolism; D055503:Protein Multimerization; D011498:Protein Precursors / Q000737:chemistry / Q000502:physiology
chemical_list: C442480:CDH23 protein, human; C418976:CDHR15 protein, mouse; C498835:CDHR15, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; C499091:Cdh23 protein, mouse; D011498:Protein Precursors
keywords: Auditory MET; Hair cell; Hearing; Lhfpl5; Mechano-electrical transduction; Pcdh15; Protocadherin-15; Tip-link; Tmc1; Tmc2; Tmhs; Tmie