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J Biol Chem
2012 Oct 19;28743:36158-67. doi: 10.1074/jbc.M112.382085.
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Dual effect of phosphatidylinositol (4,5)-bisphosphate PIP(2) on Shaker K(+) [corrected] channels.
Abderemane-Ali F, Es-Salah-Lamoureux Z, Delemotte L, Kasimova MA, Labro AJ, Snyders DJ, Fedida D, Tarek M, Baró I, Loussouarn G.
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Phosphatidylinositol (4,5)-bisphosphate (PIP(2)) is a phospholipid of the plasma membrane that has been shown to be a key regulator of several ion channels. Functional studies and more recently structural studies of Kir channels have revealed the major impact of PIP(2) on the open state stabilization. A similar effect of PIP(2) on the delayed rectifiers Kv7.1 and Kv11.1, two voltage-gated K(+) channels, has been suggested, but the molecular mechanism remains elusive and nothing is known on PIP(2) effect on other Kv such as those of the Shaker family. By combining giant-patch ionic and gating current recordings in COS-7 cells, and voltage-clamp fluorimetry in Xenopus oocytes, both heterologously expressing the voltage-dependent Shaker channel, we show that PIP(2) exerts 1) a gain-of-function effect on the maximal current amplitude, consistent with a stabilization of the open state and 2) a loss-of-function effect by positive-shifting the activation voltage dependence, most likely through a direct effect on the voltage sensor movement, as illustrated by molecular dynamics simulations.
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