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Publication : The Cation Channel TMEM63B Is an Osmosensor Required for Hearing.

First Author  Du H Year  2020
Journal  Cell Rep Volume  31
Issue  5 Pages  107596
PubMed ID  32375046 Mgi Jnum  J:303483
Mgi Id  MGI:6514514 Doi  10.1016/j.celrep.2020.107596
Citation  Du H, et al. (2020) The Cation Channel TMEM63B Is an Osmosensor Required for Hearing. Cell Rep 31(5):107596
abstractText  Hypotonic stress causes the activation of swelling-activated nonselective cation channels (NSCCs), which leads to Ca(2+)-dependent regulatory volume decrease (RVD) and adaptive maintenance of the cell volume; however, the molecular identities of the osmosensitive NSCCs remain unclear. Here, we identified TMEM63B as an osmosensitive NSCC activated by hypotonic stress. TMEM63B is enriched in the inner ear sensory hair cells. Genetic deletion of TMEM63B results in necroptosis of outer hair cells (OHCs) and progressive hearing loss. Mechanistically, the TMEM63B channel mediates hypo-osmolarity-induced Ca(2+) influx, which activates Ca(2+)-dependent K(+) channels required for the maintenance of OHC morphology. These findings demonstrate that TMEM63B is an osmosensor of the mammalian inner ear and the long-sought cation channel mediating Ca(2+)-dependent RVD.
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