Suppression of TRPC3 leads to disappearance of store-operated channels and formation of a new type of store-independent channels in A431 cells
Suppression of TRPC3 leads to disappearance of store-operated channels and formation of a new type of store-independent channels in A431 cells
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DOI：
10.1074/jbc.m608378200
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发表时间：
2007-08-10
影响因子：
4.8
通讯作者：
Mozhayeva, Galina N.
中科院分区：
文献类型：
--
作者：
Kaznacheyeva, Elena;Glushankova, Lyuba;Mozhayeva, Galina N.
在大多数不可兴奋的细胞中，钙（Ca2+）从肌醇1,4,5-三磷酸（InsP(3)）敏感的细胞内Ca2+储存中释放，通过质膜Ca2+通道偶联到Ca2+内流，其分子组成知之甚少。哺乳动物色氨酸相关蛋白家族的几个成员都与受体和储存操作的Ca2+内流有关。在这里，我们研究了原生瞬时受体电位3（TRPC3）同源物在介导A431细胞储存和受体操作的钙进入中的作用。我们发现，通过小干扰RNA （siRNA）抑制TRPC3蛋白水平可导致储存操作的钙内流显著减少，而不影响受体操作的钙内流。通过单通道分析，我们进一步证明TRPC3水平的降低会抑制特定类型的储存操作钙通道和激活储存无关的通道。我们的数据表明，TRPC3是A431细胞中功能性储存操作通道形成所必需的。
In most non-excitable cells, calcium (Ca2+) release from the inositol 1,4,5-trisphosphate (InsP(3))-sensitive intracellular Ca2+ stores is coupled to Ca2+ influx through the plasma membrane Ca2+ channels whose molecular composition is poorly understood. Several members of mammalian TRP-related protein family have been implicated to both receptor- and store-operated Ca2+ influx. Here we investigated the role of the native transient receptor potential 3(TRPC3) homologue in mediating the store- and receptor- operated calcium entry in A431 cells. We show that suppression of TRPC3 protein levels by small interfering RNA ( siRNA) leads to a significant reduction in store- operated calcium influx without affecting the receptoroperated calcium influx. With single-channel analysis, we further demonstrate that reduction of TRPC3 levels results in suppression of specific subtype of store- operated calcium channels and activation of store- independent channels. Our data suggest that TRPC3 is required for the formation of functional store-operated channels in A431 cells.