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首页> 外文期刊>Molecular and Cellular Biology >Fibrocystin/Polyductin, Found in the Same Protein Complex with Polycystin-2, Regulates Calcium Responses in Kidney Epithelia
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Fibrocystin/Polyductin, Found in the Same Protein Complex with Polycystin-2, Regulates Calcium Responses in Kidney Epithelia

机译：在与polycystin-2相同的蛋白质复合物中发现的fibrocystin / polyductin调节肾上皮细胞的钙反应。

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Recent evidence suggests that fibrocystin/polyductin (FPC), polycystin-1 (PC1), and polycystin-2 (PC2) are all localized at the plasma membrane and the primary cilium, where PC1 and PC2 contribute to fluid flow sensation and may function in the same mechanotransduction pathways. To further define the exact subcellular localization of FPC, the protein product encoded by the PKHD1 gene responsible for autosomal recessive polycystic kidney disease (PKD) in humans, and whether FPC has direct and/or indirect cross talk with PC2, which, in turn, is pivotal for the pathogenesis of autosomal dominant PKD, we performed double immunostaining and coimmunoprecipitation as well as a microfluorimetry study of kidney tubular epithelial cells. FPC and PC2 are found to completely or partially colocalize at the plasma membrane and the primary cilium and can be reciprocally coimmunoprecipitated. Although incomplete removal of FPC by small interfering RNA and antibody 803 to intracellular epitopes of FPC did not abolish flow-induced intracellular calcium responses, antibody 804 to extracellular epitopes of FPC blocked cellular calcium responses to flow stimulation. These findings suggest that FPC and polycystins share, at least in part, a common mechanotransduction pathway.
机译：最近的证据表明，纤维囊蛋白/聚管蛋白（FPC），多囊蛋白1（PC1）和多囊蛋白2（PC2）均位于质膜和初级纤毛，其中PC1和PC2有助于流体流动感觉，并可能在相同的机械转导途径。为了进一步确定FPC的确切亚细胞定位，是由 PKHD1 基因编码的蛋白产物，负责人类常染色体隐性隐性多囊肾病（PKD），以及FPC是否与之发生直接和/或间接串扰PC2反过来对于常染色体显性PKD的发病机制至关重要，因此我们对肾小管上皮细胞进行了双重免疫染色和共免疫沉淀以及微荧光分析研究。发现FPC和PC2完全或部分共定位在质膜和初级纤毛上，并且可以相互共免疫沉淀。尽管通过小分子干扰RNA不完全清除FPC和针对FPC细胞内表位的抗体803并没有消除流动诱导的细胞内钙反应，但针对FPC细胞外表位的抗体804却阻止了细胞对血流刺激的钙反应。这些发现表明，FPC和多囊藻毒素至少部分共享一条共同的机械转导途径。

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