Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. STKE, 5 August 2003
Vol. 2003, Issue 194, p. pe32
[DOI: 10.1126/stke.2003.194.pe32]

PERSPECTIVES

{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.

Abstract: Dissociation of the heterotrimeric GTP-binding protein (G protein) β{gamma} subunits from the α 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 Gβ{gamma}, intracellular Na+ can also activate the channel independently of Gβ{gamma}. Both Gβ{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 α 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, Gβ{gamma} and KACh: Old Story, New Insights. Sci. STKE 2003, pe32 (2003).

Read the Full Text



To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882