title: Vezatin, an integral membrane protein of adherens junctions, is required for the sound resilience of cochlear hair cells.
abstract: Loud sound exposure is a significant cause of hearing loss worldwide. We asked whether a lack of vezatin, an ubiquitous adherens junction protein, could result in noise-induced hearing loss. Conditional mutant mice bearing non-functional vezatin alleles only in the sensory cells of the inner ear (hair cells) indeed exhibited irreversible hearing loss after only one minute exposure to a 105 dB broadband sound. In addition, mutant mice spontaneously underwent late onset progressive hearing loss and vestibular dysfunction related to substantial hair cell death. We establish that vezatin is an integral membrane protein with two adjacent transmembrane domains, and cytoplasmic N- and C-terminal regions. Late recruitment of vezatin at junctions between MDCKII cells indicates that the protein does not play a role in the formation of junctions, but rather participates in their stability. Moreover, we show that vezatin directly interacts with radixin in its actin-binding conformation. Accordingly, we provide evidence that vezatin associates with actin filaments at cell-cell junctions. Our results emphasize the overlooked role of the junctions between hair cells and their supporting cells in the auditory epithelium resilience to sound trauma.
authors.affiliation: Institut Pasteur, Unité de Génétique et Physiologie de l'Audition, Paris, France.
authors.forename: Amel
authors.initials: A
authors.lastname: Bahloul
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Simmler
authors.forename: Vincent
authors.initials: V
authors.lastname: Michel
authors.forename: Michel
authors.initials: M
authors.lastname: Leibovici
authors.forename: Isabelle
authors.initials: I
authors.lastname: Perfettini
authors.forename: Isabelle
authors.initials: I
authors.lastname: Roux
authors.forename: Dominique
authors.initials: D
authors.lastname: Weil
authors.forename: Sylvie
authors.initials: S
authors.lastname: Nouaille
authors.forename: Jian
authors.initials: J
authors.lastname: Zuo
authors.forename: Cristina
authors.initials: C
authors.lastname: Zadro
authors.forename: Danilo
authors.initials: D
authors.lastname: Licastro
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
authors.forename: Paul
authors.initials: P
authors.lastname: Avan
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hardelin
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
mesh_terms: D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism*; D000375:Aging / Q000473:pathology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D016923:Cell Death; D002460:Cell Line; D003051:Cochlea / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004285:Dogs; D006198:Hair Cells, Auditory / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D018069:Hair Cells, Vestibular / Q000473:pathology / Q000648:ultrastructure; D034381:Hearing Loss / Q000473:pathology / Q000503:physiopathology; D019426:Integrases / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009622:Noise; D017084:Otoacoustic Emissions, Spontaneous; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013016:Sound
chemical_list: D000199:Actins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C506603:vezatin protein, mouse; C071776:radixin; C045073:Cre recombinase; D019426:Integrases; D002118:Calcium