The TRPM7 channel is inactivated by PIP2 hydrolysis

被引:416
作者
Runnels, LW [1 ]
Yue, LX [1 ]
Clapham, DE [1 ]
机构
[1] Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA
关键词
D O I
10.1038/ncb781
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
TRPM7 (ChaK1, TRP-PLIK, LTRPC7) is a ubiquitous, calcium-permeant ion channel that is unique in being both an ion channel and a serine/threonine kinase. The kinase domain of TRPM7 directly associates with the C2 domain of phospholipase C ( PLC). Here, we show that in native cardiac cells and heterologous expression systems, Galphaq-linked receptors or tyrosine kinase receptors that activate PLC potently inhibit channel activity. Numerous experimental approaches demonstrated that phosphatidylinositol 4,5-bisphosphate (PIP2), the substrate of PLC, is a key regulator of TRPM7. We conclude that receptor-mediated activation of PLC results in the hydrolysis of localized PIP2, leading to inactivation of the TRPM7 channel.
引用
收藏
页码:329 / 336
页数:8
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