Vezatin, an integral membrane protein of adherens junctions, is required for the sound resilience of cochlear hair cells

Amel Bahloul, Marie Christine Simmler, Vincent Michel, Michel Leibovici, Isabelle Perfettini, Isabelle Roux, Dominique Weil, Sylvie Novaille, Jian Zuo, Cristina Zadro, Danilo Licastro, Paolo Gasparini, Paul Auan, Jean Pierre Hardelin, Christine Petit

Research output: Contribution to journalArticle

Abstract

Loud sound exposure is a significant cause of hearing loss worldwide. We asked whethera 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.

Original languageEnglish
Pages (from-to)125-138
Number of pages14
JournalEMBO Molecular Medicine
Volume1
Issue number2
DOIs
Publication statusPublished - May 2009

Fingerprint

Auditory Hair Cells
Adherens Junctions
Membrane Proteins
Hearing Loss
Inner Auditory Hair Cells
Noise-Induced Hearing Loss
Intercellular Junctions
Inner Ear
Actin Cytoskeleton
Actins
Proteins
Cell Death
Epithelium
Alleles
Wounds and Injuries

Keywords

  • Adherens junction
  • Mouse model
  • Noise-induced hearing loss
  • Organ of Corti
  • Vezatin

ASJC Scopus subject areas

  • Molecular Medicine

Cite this

Bahloul, A., Simmler, M. C., Michel, V., Leibovici, M., Perfettini, I., Roux, I., ... Petit, C. (2009). Vezatin, an integral membrane protein of adherens junctions, is required for the sound resilience of cochlear hair cells. EMBO Molecular Medicine, 1(2), 125-138. https://doi.org/10.1002/emmm.200900015

Vezatin, an integral membrane protein of adherens junctions, is required for the sound resilience of cochlear hair cells. / Bahloul, Amel; Simmler, Marie Christine; Michel, Vincent; Leibovici, Michel; Perfettini, Isabelle; Roux, Isabelle; Weil, Dominique; Novaille, Sylvie; Zuo, Jian; Zadro, Cristina; Licastro, Danilo; Gasparini, Paolo; Auan, Paul; Hardelin, Jean Pierre; Petit, Christine.

In: EMBO Molecular Medicine, Vol. 1, No. 2, 05.2009, p. 125-138.

Research output: Contribution to journalArticle

Bahloul, A, Simmler, MC, Michel, V, Leibovici, M, Perfettini, I, Roux, I, Weil, D, Novaille, S, Zuo, J, Zadro, C, Licastro, D, Gasparini, P, Auan, P, Hardelin, JP & Petit, C 2009, 'Vezatin, an integral membrane protein of adherens junctions, is required for the sound resilience of cochlear hair cells', EMBO Molecular Medicine, vol. 1, no. 2, pp. 125-138. https://doi.org/10.1002/emmm.200900015
Bahloul, Amel ; Simmler, Marie Christine ; Michel, Vincent ; Leibovici, Michel ; Perfettini, Isabelle ; Roux, Isabelle ; Weil, Dominique ; Novaille, Sylvie ; Zuo, Jian ; Zadro, Cristina ; Licastro, Danilo ; Gasparini, Paolo ; Auan, Paul ; Hardelin, Jean Pierre ; Petit, Christine. / Vezatin, an integral membrane protein of adherens junctions, is required for the sound resilience of cochlear hair cells. In: EMBO Molecular Medicine. 2009 ; Vol. 1, No. 2. pp. 125-138.
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