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 language | English |
|---|---|
| Pages (from-to) | 125-138 |
| Number of pages | 14 |
| Journal | EMBO Molecular Medicine |
| Volume | 1 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - May 2009 |
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Keywords
- Adherens junction
- Mouse model
- Noise-induced hearing loss
- Organ of Corti
- Vezatin
ASJC Scopus subject areas
- Molecular Medicine
Cite this
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 journal › Article
}
TY - JOUR
T1 - Vezatin, an integral membrane protein of adherens junctions, is required for the sound resilience of cochlear hair cells
AU - Bahloul, Amel
AU - Simmler, Marie Christine
AU - Michel, Vincent
AU - Leibovici, Michel
AU - Perfettini, Isabelle
AU - Roux, Isabelle
AU - Weil, Dominique
AU - Novaille, Sylvie
AU - Zuo, Jian
AU - Zadro, Cristina
AU - Licastro, Danilo
AU - Gasparini, Paolo
AU - Auan, Paul
AU - Hardelin, Jean Pierre
AU - Petit, Christine
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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.
KW - Adherens junction
KW - Mouse model
KW - Noise-induced hearing loss
KW - Organ of Corti
KW - Vezatin
UR - http://www.scopus.com/inward/record.url?scp=77953658421&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953658421&partnerID=8YFLogxK
U2 - 10.1002/emmm.200900015
DO - 10.1002/emmm.200900015
M3 - Article
C2 - 20049712
AN - SCOPUS:77953658421
VL - 1
SP - 125
EP - 138
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
SN - 1757-4676
IS - 2
ER -