Science · 2006 · 508 citations · 23 references
Life SciencesBiochemistryCell BiologyCell SignalingElectrophysiologySignal TransductionIon Channel PhysiologyIon Channel RegulationIon Channel SignalingIon ChannelsPhosphoinositide SignalingProtein PhosphorylationEnzymesPhosphatidylinositol 3, 4, 5-Trisphosphate SignalingPhosphatidylinositol 4, 5-BisphosphatePhosphoinositide PhosphorylationPhosphoinositide Regulation Of Ion ChannelsPhospholipase C PathwayPhospholipase C SignalingPhospholipase-mediated Signal Transduction
To resolve the controversy about messengers regulating KCNQ ion channels during phospholipase C-mediated suppression of current, we designed translocatable enzymes that quickly alter the phosphoinositide composition of the plasma membrane after application of a chemical cue. The KCNQ current falls rapidly to zero when phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2 or PI(4,5)P2] is depleted without changing Ca2+, diacylglycerol, or inositol 1,4,5-trisphosphate. Current rises by 30% when PI(4,5)P2 is overproduced and does not change when phosphatidylinositol 3,4,5-trisphosphate is raised. Hence, the depletion of PI(4,5)P2 suffices to suppress current fully, and other second messengers are not needed. Our approach is ideally suited to study biological signaling networks involving membrane phosphoinositides.
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Controlling Signal Transduction with Synthetic Ligands
David M. Spencer, Thomas J. Wandless, Stuart L. Schreiber et al. · Science · 1993 · 854 citations