Functional cooperation between two otoconial proteins Oc90 and Nox3.
Functional cooperation between two otoconial proteins Oc90 and Nox3.
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DOI：
10.3233/ves-201591
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Lundberg YW
中科院分区：
文献类型：
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作者：
Xu Y;Yang L;Zhao X;Zhang Y;Jones TA;Jones SM;Lundberg YW
耳鸣相关的眩晕和平衡障碍在人类中很常见，但其分子病因目前尚不清楚。为了研究耳石形成和维持的机制，我们研究了耳石形成的主要组成蛋白Oc90和耳石形成所必需的调控蛋白NADPH氧化酶Nox3在功能上是否连锁。我们进行了平衡行为、电生理、形态和分子细胞分析。Oc90和Nox3的双杂合突变小鼠表现出严重的不平衡，尽管没有双零突变那么严重。相比之下，单个杂合子突变小鼠的平衡能力正常。双杂合子小鼠有耳锥缺陷，双缺位小鼠没有耳锥。此外，后一组小鼠的一些毛束经历了加速退化。体外钙化分析表明，稳定表达这两种蛋白的细胞在双转染细胞中的钙化强度要强得多。Oc90和Nox3相互增强功能，这不仅对耳锥的形成至关重要，而且对毛束的维护也是至关重要的。
Otoconia-related vertigo and balance deficits are common in humans, but the molecular etiology is unknown at present. In order to study mechanisms of otoconia formation and maintenance, we have investigated whether otoconin-90 (Oc90), the predominant otoconial constituent protein, and the NADPH oxidase Nox3, an essential regulatory protein for otoconia formation, are functionally interlinked. We performed balance behavioral, electrophysiological, morphological and molecular cellular analyses. Double heterozygous mutant mice for Oc90 and Nox3 show severe imbalance, albeit less profound than double null mutants. In contrast, single heterozygous mutant mice have normal balance. Double heterozygous mice have otoconia defects and double null mice have no otoconia. In addition, some hair bundles in the latter mice go through accelerated degeneration. In vitro calcification analysis in cells stably expressing these proteins singly and doubly shows much more intense calcification in the double transfectants. Oc90 and Nox3 augment each other’s function, which is not only critical for otoconia formation but also for hair bundle maintenance.