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Inositol lipids and TRPC channel activation

机译：肌醇脂质和TRPC通道激活

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The original hypothesis put forth by Bob Michell in his seminal 1975 review held that inositol lipid breakdown was involved in the activation of plasma membrane calcium channels or 'gates'. Subsequently, it was demonstrated that while the interposition of inositol lipid breakdown upstream of calcium signalling was correct, it was predominantly the release of Ca~(2+) that was activated, through the formation of Ins(l,4,5)P_3. Ca~(2+) entry across the plasma membrane involved a secondary mechanism signalled in an unknown manner by depletion of intracellular Ca~(2+) stores. In recent years, however, additional non-store-operated mechanisms for Ca~(2+) entry have emerged. In many instances, these pathways involve homologues of the Drosophila trp (transient receptor potential) gene. In mammalian systems there are seven members of the TRP superfamily, designated TRPC1-TRPC7, which appear to be reasonably close structural and functional homologues of Drosophila TRP. Although these channels can sometimes function as store-operated channels, in the majority of instances they function as channels more directly linked to phospholipase C activity. Three members of this family, TRPC3, 6 and 7, are activated by the phosphoinositide breakdown product, diacylglycerol. Two others, TRPC4 and 5, are also activated as a consequence of phospholipase C activity, although the precise substrate or product molecules involved are still unclear. Thus the TRPCs represent a family of ion channels that are directly activated by inositol lipid breakdown, confirming Bob Michell's original prediction 30 years ago.
机译：由Bob Michell在他的精英1975年审查中提出的原始假设认为，肌醇脂质分解涉及激活血浆膜钙通道或“门”。随后，据证明，虽然钙信号传导上游的肌醇脂分解的插入是正确的，但是通过形成INS（L，4,5）P_3，它主要是活化的Ca〜（2+）的释放。跨等离子体膜的Ca〜（2+）入口涉及通过细胞内Ca〜（2+）商店的未知方式以未知方式发出的二次机制。然而，近年来，出现了CA〜（2+）条目的额外非商店操作机制。在许多情况下，这些途径涉及果蝇TRP（瞬态受体电位）基因的同源物。在哺乳动物系统中，TRP超家族的七名成员被指定的TRPC1-TRPC7，这似乎是合理的果蝇TRP的结构和功能性同源物。虽然这些通道有时可以用作储存的通道，但在大多数情况下，它们用作更直接与磷脂酶C活动相关的通道。该系列的三个成员TRPC3,6和7，由磷酸阳性崩解产品，二酰基甘油激活。除了磷脂酶C活性的结果，还可以激活另外两种，尽管所涉及的精确底物或产物分子仍然不清楚。因此，TRPC代表了由肌醇脂分解直接激活的离子通道系列，在30年前确认Bob Michell的原始预测。

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