Fibrocystin/polyductin, found in the same protein complex with polycystin-2, regulates calcium responses in kidney epithelia
Fibrocystin/polyductin, found in the same protein complex with polycystin-2, regulates calcium responses in kidney epithelia
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DOI：
10.1128/mcb.00072-07
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发表时间：
2007-04-01
影响因子：
5.3
通讯作者：
Zhou, Jing
中科院分区：
文献类型：
--
作者：
Wang, Shixuan;Zhang, Jingjing;Zhou, Jing
最近的证据表明，纤维囊蛋白/多导管蛋白（FPC）、多囊蛋白-1（PC 1）和多囊蛋白-2（PC 2）都位于质膜和初级纤毛上，其中PC 1和PC 2有助于液体感觉，并且可能在相同的机械传导途径中发挥作用。为了进一步确定FPC的确切亚细胞定位，FPC是由PKHD 1基因编码的蛋白产物，负责人类常染色体隐性多囊肾病（PKD），以及FPC是否与PC 2直接和/或间接串扰，而PC 2反过来又是常染色体显性PKD发病机制的关键，我们对肾小管上皮细胞进行了双重免疫染色和免疫共沉淀以及显微荧光分析研究。FPC和PC 2被发现完全或部分共定位于质膜和初级纤毛，并且可以被免疫共沉淀。虽然不完全去除FPC的小干扰RNA和抗体803细胞内表位的FPC没有废除如何诱导的细胞内钙反应，抗体804细胞外表位的FPC阻断细胞钙反应的流动刺激。这些研究结果表明，FPC和多囊蛋白共享，至少部分，一个共同的机械转导途径。
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 How 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 How-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.