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Coupling mechanism of a GPCR and a heterotrimeric G protein during chemoattractant gradient sensing in Dictyostelium.

Xu, Xuehua ; Meckel, Tobias ; Brzostowski, Joseph A. ; Yan, Jianshe ; Meier-Schellersheim, Martin ; Jin, Tian (2010)
Coupling mechanism of a GPCR and a heterotrimeric G protein during chemoattractant gradient sensing in Dictyostelium.
In: Science signaling, 3 (141)
Article, Bibliographie

Abstract

The coupling of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) with G proteins is fundamental for GPCR signaling; however, the mechanism of coupling is still debated. Moreover, how the proposed mechanisms affect the dynamics of downstream signaling remains unclear. Here, through experiments involving fluorescence recovery after photobleaching and single-molecule imaging, we directly measured the mobilities of cyclic adenosine monophosphate (cAMP) receptor 1 (cAR1), a chemoattractant receptor, and a G protein βγ subunit in live cells. We found that cAR1 diffused more slowly in the plasma membrane than did Gβγ. Upon binding of ligand to the receptor, the mobility of cAR1 was unchanged, whereas the speed of a fraction of the faster-moving Gβγ subunits decreased. Our measurements showed that cAR1 was relatively immobile and Gβγ diffused freely, suggesting that chemoattractant-bound cAR1 transiently interacted with G proteins. Using models of possible coupling mechanisms, we computed the temporal kinetics of G protein activation. Our fluorescence resonance energy transfer imaging data showed that fully activated cAR1 induced the sustained dissociation of G protein α and βγ subunits, which indicated that ligand-bound cAR1 activated G proteins continuously. Finally, simulations indicated that a high-affinity coupling of ligand-bound receptors and G proteins was essential for cAR1 to translate extracellular gradient signals into directional cellular responses. We suggest that chemoattractant receptors use a ligand-induced coupling rather than a precoupled mechanism to control the activation of G proteins during chemotaxis.

Item Type: Article
Erschienen: 2010
Creators: Xu, Xuehua ; Meckel, Tobias ; Brzostowski, Joseph A. ; Yan, Jianshe ; Meier-Schellersheim, Martin ; Jin, Tian
Type of entry: Bibliographie
Title: Coupling mechanism of a GPCR and a heterotrimeric G protein during chemoattractant gradient sensing in Dictyostelium.
Language: English
Date: 2010
Journal or Publication Title: Science signaling
Volume of the journal: 3
Issue Number: 141
Abstract:

The coupling of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) with G proteins is fundamental for GPCR signaling; however, the mechanism of coupling is still debated. Moreover, how the proposed mechanisms affect the dynamics of downstream signaling remains unclear. Here, through experiments involving fluorescence recovery after photobleaching and single-molecule imaging, we directly measured the mobilities of cyclic adenosine monophosphate (cAMP) receptor 1 (cAR1), a chemoattractant receptor, and a G protein βγ subunit in live cells. We found that cAR1 diffused more slowly in the plasma membrane than did Gβγ. Upon binding of ligand to the receptor, the mobility of cAR1 was unchanged, whereas the speed of a fraction of the faster-moving Gβγ subunits decreased. Our measurements showed that cAR1 was relatively immobile and Gβγ diffused freely, suggesting that chemoattractant-bound cAR1 transiently interacted with G proteins. Using models of possible coupling mechanisms, we computed the temporal kinetics of G protein activation. Our fluorescence resonance energy transfer imaging data showed that fully activated cAR1 induced the sustained dissociation of G protein α and βγ subunits, which indicated that ligand-bound cAR1 activated G proteins continuously. Finally, simulations indicated that a high-affinity coupling of ligand-bound receptors and G proteins was essential for cAR1 to translate extracellular gradient signals into directional cellular responses. We suggest that chemoattractant receptors use a ligand-induced coupling rather than a precoupled mechanism to control the activation of G proteins during chemotaxis.

Divisions: 10 Department of Biology
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10 Department of Biology > Plant Membrane Biophyscis (20.12.23 renamed in Biology of Algae and Protozoa)
10 Department of Biology > Membrane Dynamics
Date Deposited: 06 Jun 2011 13:04
Last Modified: 08 Jun 2020 07:26
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