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 beta gamma from plasma membrane to endomembranes on receptor activation attenuated this response. A FRET based G protein sensor suggested that in contrast to translocating G beta gamma, non- translocating G beta gamma 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 beta gamma translocation are thus unanticipated modulators of the intensity of a cell's response to an extracellular signal.
G Protein Subunit Dissociation and Translocation Regulate Cellular Response to Receptor Stimulation
CHISARI, Mariangela;
2009-01-01
Abstract
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 beta gamma from plasma membrane to endomembranes on receptor activation attenuated this response. A FRET based G protein sensor suggested that in contrast to translocating G beta gamma, non- translocating G beta gamma 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 beta gamma translocation are thus unanticipated modulators of the intensity of a cell's response to an extracellular signal.File | Dimensione | Formato | |
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