G protein subunit dissociation and translocation regulate cellular response to receptor stimulation.
We examined the role of G proteins in modulating the response of living cells to receptor activation. The response of an effector, phospholipase C-beta to M3 muscarinic receptor activation was measured using sensors that detect the generation of inositol triphosphate or diacylglycerol. The recently discovered translocation of G betagamma from plasma membrane to endomembranes on receptor activation attenuated this response. A FRET based G protein sensor suggested that in contrast to translocating G betagamma, non-translocating G betagamma subunits do not dissociate from the alpha q subunit on receptor activation leading to prolonged retention of the heterotrimer state and an accentuated response. M3 receptors with tethered alpha q induced differential responses to receptor activation in cells with or without an endogenous translocation capable gamma subunit. G protein heterotrimer dissociation and betagamma translocation are thus unanticipated modulators of the intensity of a cell's response to an extracellular signal.
Chisari
Mariangela
M
Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Saini
Deepak Kumar
DK
Cho
Joon-Ho
JH
Kalyanaraman
Vani
V
Gautam
N
N
D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D019281:Dimerization; D031541:Fluorescence Resonance Energy Transfer; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D005786:Gene Expression Regulation; D008954:Models, Biological; D054799:Phospholipase C beta / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D043587:Receptor, Muscarinic M3 / Q000378:metabolism
D043587:Receptor, Muscarinic M3; D054799:Phospholipase C beta; D019204:GTP-Binding Proteins