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Sci. STKE, 14 May 2002
Vol. 2002, Issue 132, p. tw174
[DOI: 10.1126/stke.2002.132.tw174]

EDITORS' CHOICE

TRP Ion Channels Dual Action of PIP2

Activation of some TRP-type calcium ion channels requires activation of phospholipase C (PLC) and hydrolysis of its substrate phosphatidylinositol 4,5-bisphosphate (PIP2). This cascade is initiated when certain heterotrimeric guanine nucleotide-biding protein (G protein)-coupled receptors are activated. But Runnels et al. report the deviant behavior of one family member, TRPM7. Activation of either a G-protein-coupled receptor or a receptor tyrosine kinase actually inhibited TRPM7 through the same signaling pathway of PIP2 hydrolysis through PLC. TRPM7 coimmunoprecipitated with PLC-β2 when the two proteins were overexpressed in cultured cells. The inhibitory effect of PIP2 on TRPM7 channel currents was blocked by the presence of antibodies against PIP2. Activation of the G-protein-coupled receptor for lysophophatidic acid in cardiac myocytes also inhibited endogenous TRPM7 activity. ATP and magnesium have also been implicated in regulating TRPM7 but it is presently unclear how any of these molecules directly modulate channel activity. The authors propose that the activating or inhibitory nature of PIP2 on TRP-type channels may depend on the proximity of specific PLC isoforms to TRP channels.

L. W. Runnels, L. Xie, D. E. Clapham, The TRPM7 channel is inactivated by PIP2 hydrolysis. Nature Cell Biol. 4, 32-336 (2002). [Online Journal]

Citation: Dual Action of PIP2. Sci. STKE 2002, tw174 (2002).


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