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首页> 外文期刊>Cellular Physiology and Biochemistry >Polycystin-1, 2, and STIM1 Interact with IP3R to Modulate ER Ca2+ Release through the PI3K/Akt Pathway
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Polycystin-1, 2, and STIM1 Interact with IP3R to Modulate ER Ca2+ Release through the PI3K/Akt Pathway

机译：Polycystin-1、2和STIM1与IP3R相互作用以通过PI3K / Akt途径调节ER Ca2 +释放

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Dysregulation of Casup2+/sup signaling and homeostasis has been linked to the development of ADPKD through aberrant functioning of the polycystins. In this study, we investigated the role of the polycystins in modulating Casup2+/sup signaling. Expression of full-length PC1 in MDCK cells inhibited intracellular Casup2+/sup release in response to ATP when compared to control cells. This phenotype correlated with reduced interaction of endogenous PC2 and IPsub3/subR in PC1-containing cells. We also found that endogenous STIM1 also interacted with the IPsub3/subR, and this interaction was enhanced by PC1 expression. Increased interaction between STIM1 and IPsub3/subR inhibited Casup2+/sup release. PC1 regulates intracellular Casup2+/sup release and the interaction of PC2-IPsub3/subR-STIM1 through the PI3K/Akt signaling pathway. Inhibition of the PI3K/Akt pathway in PC1 containing cells restored intracellular Casup2+/sup release, increased the interaction between PC2 and IPsub3/subR and disrupted the STIM1-IPsub3/subR complex. Conversely, activation of the PI3K/Akt signaling pathway by HGF in control MDCK cells gave the reverse effects. It reduced the release of Casup2+/sup to levels comparable to the PC1 cells, inhibited the association PC2 and IPsub3/subR, and increased the interaction between STIM and IPsub3/subR. Overall, our studies provide a potential mechanism for the modulation of intracellular Casup2+/sup signaling by the polycystins.
机译：Ca 2 + 信号通路的失调和体内平衡通过多囊藻蛋白的异常功能与ADPKD的发展有关。在这项研究中，我们研究了多囊藻毒素在调节Ca 2 + 信号传导中的作用。与对照细胞相比，MDCK细胞中全长PC1的表达抑制了细胞内Ca 2 + 对ATP的释放。该表型与内源性PC2和IP1 3 R在含PC1的细胞中减少的相互作用有关。我们还发现内源性STIM1也与IP 3 R相互作用，并且这种相互作用被PC1表达增强。 STIM1与IP 3 R之间相互作用增强，抑制了Ca 2 + 的释放。 PC1通过PI3K / Akt信号通路调节细胞内Ca 2 + 的释放以及PC2-IP 3 R-STIM1的相互作用。抑制PC1细胞中PI3K / Akt通路可恢复细胞内Ca 2 + 释放，增加PC2与IP 3 R之间的相互作用并破坏STIM1-IP 3 复合物。相反，在对照MDCK细胞中，HGF对PI3K / Akt信号通路的激活产生了相反的作用。它可以将Ca 2 + 的释放降低到与PC1细胞相当的水平，抑制PC2和IP 3 R的缔合，并增加STIM和IP 之间的相互作用。 3 R。总体而言，我们的研究为多囊藻蛋白调节细胞内Ca 2 + 信号传导提供了潜在的机制。

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