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Sci. STKE, 5 August 2003
[DOI: 10.1126/stke.2003.194.pe32]

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Gß{gamma} and KACh: Old Story, New Insights

Tooraj Mirshahi, Taihao Jin, and Diomedes E. Logothetis*

Department of Physiology and Biophysics, Mt. Sinai School of Medicine, New York University, New York, NY 10029, USA.

Summary: Dissociation of the heterotrimeric GTP-binding protein (G protein) ß{gamma} subunits from the {alpha} subunit is a prerequisite step in the ability of these proteins to signal to downstream effectors. There is evidence that ions such as Na+ and Cl- can facilitate this dissociation. Interestingly, for KACh, the first known effector for Gß{gamma}, intracellular Na+ can also activate the channel independently of Gß{gamma}. Both Gß{gamma} and Na+ strengthen channel interactions with the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2), an event thought to be essential in opening the channel. PIP2 interacts with channel regions that form a binding pocket proximal to the transmembrane domains and is likely to exert a tangential, pulling force to mechanically open a gate at the cytoplasmic face of the channel pore. The tangential force generated by channel-PIP2 interactions is the likely force behind gating in all inwardly rectifying K+ channels. The gate opens when the lower part of the pore-lining transmembrane {alpha} helix pivots around a glycine residue in the middle of the helix. This mechanism of channel gating is conserved among K+ channels from bacteria to mammals and may represent a common mechanism for K+ channel gating.

*Corresponding author. Phone: 212-241-6284, E-mail: diomedes.logothetis{at}mssm.edu

Citation: T. Mirshahi, T. Jin, D. E. Logothetis, Gß{gamma} and KACh: Old Story, New Insights. Sci. STKE 2003, pe32 (2003).

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Science Signaling. ISSN 1937-9145 (pre-2008: Science's STKE. ISSN 1525-8882)