G beta gamma and KACh: old story, new insights.
Dissociation of the heterotrimeric GTP-binding protein (G protein) betagamma 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 Gbetagamma, intracellular Na+ can also activate the channel independently of Gbetagamma. Both Gbetagamma 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.
Mirshahi
Tooraj
T
Department of Physiology and Biophysics, Mt. Sinai School of Medicine, New York University, New York, NY 10029, USA.
Jin
Taihao
T
Logothetis
Diomedes E
DE
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D015398:Signal Transduction / Q000502:physiology*
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D020962:Heterotrimeric GTP-Binding Proteins