The Cation Channel TMEM63B Is an Osmosensor Required for Hearing
The Cation Channel TMEM63B Is an Osmosensor Required for Hearing
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阳离子通道 TMEM63B 是听力所需的渗透传感器
DOI：
10.1016/j.celrep.2020.107596
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发表时间：
2020-05-05
期刊：
影响因子：
8.8
通讯作者：
Shi, Yun Stone
中科院分区：
文献类型：
--
作者：
Du, Han;Ye, Chang;Shi, Yun Stone
低渗应激引起膨胀激活的非选择性阳离子通道（NSCC）的激活，这导致Ca 2+依赖性调节体积减小（RVD）和细胞体积的适应性维持;然而，对钙离子敏感的NSCC的分子身份仍不清楚。在此，我们鉴定TMEM 63 B为低渗应激激活的钙离子敏感的NSCC。TMEM 63 B在内耳感觉毛细胞中富集。TMEM 33 B的基因缺失导致外毛细胞（OHC）的坏死性凋亡和进行性听力损失。在机制上，TMEM 63 B通道介导低渗透压诱导的Ca 2+内流，其激活维持OHC形态所需的Ca 2+依赖性K+通道。这些发现表明，TMEM 63 B是哺乳动物内耳的Ca 2+传感器和长期寻求的阳离子通道介导的Ca 2+依赖性RVD。
Hypotonic stress causes the activation of swelling-activated nonselective cation channels (NSCCs), which leads to Ca2+-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 TMEM33B results in necroptosis of outer hair cells (OHCs) and progressive hearing loss. Mechanistically, the TMEM63B channel mediates hypo-osmolarity-induced Ca2+ influx, which activates Ca2+-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 Ca2+-dependent RVD.