g protein subunit dissociation and translocation regulate cellular response to receptor stimulationg蛋白亚基解离和易位对受体刺激调节细胞反应.pdfVIP

G Protein Subunit Dissociation and Translocation Regulate Cellular Response to Receptor Stimulation 1 1 1 1 1,2 Mariangela Chisari , Deepak Kumar Saini , Joon-Ho Cho , Vani Kalyanaraman , N. Gautam * 1 Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, United States of America, 2 Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America 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-b to M3 muscarinic receptor activation was measured using sensors that detect the generation of inositol triphosphate or diacylglycerol. The recently discovered translocation of Gbc from plasma membrane to endomembranes on receptor activation attenuated this response. A FRET based G protein sensor suggested that in contrast to translocating Gbc, non-translocating Gbc subunits do not dissociate from the aq subunit on receptor activation leading to prolonged retention of the heterotrimer state and an accentuated response. M3 receptors with tethered aq induced differential responses to receptor activation in cells with or without an endogenous translocation capable c subunit. G protein heterotrimer dissociation and bc translocation are thus unanticipated modulators of the intensity of a cell’s response to an extracellular signal. Citation: Chisari M, Saini DK, Cho J-H, Kalyanaraman V, Gautam N (2009) G Protein Subunit Dissociation and Translocation Regulate Cellular Response to Re