Regulation of Cellular Calcium in Vestibular Supporting Cells by Otopetrin 1
Regulation of Cellular Calcium in Vestibular Supporting Cells by Otopetrin 1
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DOI：
10.1152/jn.00525.2010
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发表时间：
2010-12-01
影响因子：
2.5
通讯作者：
Ornitz, David M.
中科院分区：
文献类型：
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作者：
Kim, Euysoo;Hyrc, Krzysztof L.;Ornitz, David M.
Kim E，Hyrc KL，Speck J，Lundberg YW，Salles FT，Kachar B，Goldberg MP，Warchol ME，Ornitz DM.耳啡肽1对前庭支持细胞内钙离子的调节。J Neurophysiol 104：3439-3450，2010.首次发表于2010年6月16日; doi：10.1152/jn.00525.2010。OTOP 1是一种多跨膜结构域蛋白，对耳石的矿化、前庭功能所需的碳酸钙生物矿物质和正常的重力感觉至关重要。耳石矿化的驱动机制知之甚少，但有人提出，支持细胞和维持高浓度钙的机制是至关重要的。使用OTOP 1基因敲除小鼠和椭圆囊上皮器官培养系统，我们发现OTOP 1在支持细胞的顶端表达，并在响应嘌呤能激动剂（如腺苷5 '-三磷酸（ATP））时起增加胞浆钙的作用。这是通过以细胞外钙依赖性方式阻断钙从细胞内储存的动员和介导细胞外钙的流入来实现的。这些数据支持一个模型，其中OTOP 1作为传感器的细胞外钙浓度附近的支持细胞和响应ATP的内淋巴液中，以增加细胞内钙水平在耳石矿化。
Kim E, Hyrc KL, Speck J, Lundberg YW, Salles FT, Kachar B, Goldberg MP, Warchol ME, Ornitz DM. Regulation of cellular calcium in vestibular supporting cells by Otopetrin 1. J Neurophysiol 104: 3439-3450, 2010. First published June 16, 2010; doi:10.1152/jn.00525.2010. Otopetrin 1 (OTOP1) is a multitrans-membrane domain protein, which is essential for mineralization of otoconia, the calcium carbonate biominerals required for vestibular function, and the normal sensation of gravity. The mechanism driving mineralization of otoconia is poorly understood, but it has been proposed that supporting cells and a mechanism to maintain high concentrations of calcium are critical. Using Otop1 knockout mice and a utricular epithelial organ culture system, we show that OTOP1 is expressed at the apex of supporting cells and functions to increase cytosolic calcium in response to purinergic agonists, such as adenosine 5'-triphosphate (ATP). This is achieved by blocking mobilization of calcium from intracellular stores in an extracellular calcium-dependent manner and by mediating influx of extracellular calcium. These data support a model in which OTOP1 acts as a sensor of the extracellular calcium concentration near supporting cells and responds to ATP in the endolymph to increase intracellular calcium levels during otoconia mineralization.