活细胞中的G蛋白偶联受体信号复合体
G protein coupled receptor signaling complexes in live cells.
作者信息
Hepler John R
机构信息
Department of Pharmacology; Emory University School of Medicine; Atlanta, GA USA.
出版信息
Cell Logist. 2014 Jun 4;4:e29392. doi: 10.4161/cl.29392. eCollection 2014.
Abstract
Classical models of receptor (GPCR) and G protein (Gαβγ) signaling based on biochemical studies have proposed that receptor stimulation results in G protein activation (Gα-GTP) and dissociation of the heterotrimer (Gα-GTP + Gβγ) to regulate downstream signaling events. Unclear is whether or not there exists freely diffusible, activated Gα-GTP on cellular membranes capable of catalytic signal amplification. Recent studies in live cells indicate that GPCRs serve as platforms for the assembly of macromolecular signaling complexes that include G proteins to support a highly efficient and spatially restricted signaling event, with no requirement for full Gα-GTP and Gβγ dissociation and lateral diffusion within the plasma membrane.
摘要
基于生化研究的受体（GPCR）和G蛋白（Gαβγ）信号传导经典模型提出，受体刺激会导致G蛋白激活（Gα-GTP）以及异源三聚体解离（Gα-GTP + Gβγ），从而调节下游信号事件。目前尚不清楚细胞膜上是否存在能够催化信号放大的可自由扩散的活化Gα-GTP。近期对活细胞的研究表明，GPCR作为大分子信号复合物组装的平台，这些复合物包括G蛋白，以支持高效且空间受限的信号事件，而无需Gα-GTP和Gβγ在质膜内完全解离和侧向扩散。
相似文献
1
G protein coupled receptor signaling complexes in live cells.
Cell Logist. 2014 Jun 4;4:e29392. doi: 10.4161/cl.29392. eCollection 2014.
2
The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits.
Int J Biol Sci. 2005;1(2):51-66. doi: 10.7150/ijbs.1.51. Epub 2005 Apr 1.
3
A historical perspective on the lateral diffusion model of GTPase activation and related coupling of membrane signaling proteins.
Cell Logist. 2014 Jun 4;4:e29389. doi: 10.4161/cl.29389. eCollection 2014.
4
RGS14 regulates the lifetime of G-GTP signaling but does not prolong G signaling following receptor activation in live cells.
Pharmacol Res Perspect. 2016 Aug 18;4(5):e00249. doi: 10.1002/prp2.249. eCollection 2016 Oct.
5
Introduction: G Protein-coupled Receptors and RGS Proteins.
Prog Mol Biol Transl Sci. 2015;133:1-11. doi: 10.1016/bs.pmbts.2015.03.002. Epub 2015 Apr 8.
6
G protein-coupled receptors and resistance to inhibitors of cholinesterase-8A (Ric-8A) both regulate the regulator of g protein signaling 14 RGS14·Gαi1 complex in live cells.
J Biol Chem. 2011 Nov 4;286(44):38659-38669. doi: 10.1074/jbc.M111.274928. Epub 2011 Aug 31.
7
Gbetagamma inhibits Galpha GTPase-activating proteins by inhibition of Galpha-GTP binding during stimulation by receptor.
J Biol Chem. 2006 Feb 24;281(8):4746-53. doi: 10.1074/jbc.M510573200. Epub 2005 Dec 29.
8
Backbone resonance assignments for G protein α(i3) subunit in the GTP-bound state.
Biomol NMR Assign. 2012 Oct;6(2):217-20. doi: 10.1007/s12104-012-9361-6. Epub 2012 Jan 25.
9
Gβγ signaling to the chemotactic effector P-REX1 and mammalian cell migration is directly regulated by Gα and Gα proteins.
J Biol Chem. 2019 Jan 11;294(2):531-546. doi: 10.1074/jbc.RA118.006254. Epub 2018 Nov 16.
10
Re-examining the 'Dissociation Model' of G protein activation from the perspective of Gβγ signaling.
FEBS J. 2021 Apr;288(8):2490-2501. doi: 10.1111/febs.15605. Epub 2020 Nov 16.
引用本文的文献
1
G protein-coupled receptor-effector macromolecular membrane assemblies (GEMMAs).
Pharmacol Ther. 2022 Mar;231:107977. doi: 10.1016/j.pharmthera.2021.107977. Epub 2021 Sep 1.
2
A short C-terminal peptide in Gγ regulates Gβγ signaling efficacy.
Mol Biol Cell. 2021 Aug 1;32(16):1446-1458. doi: 10.1091/mbc.E20-11-0750. Epub 2021 Jun 9.
3
Gβγ signaling to the chemotactic effector P-REX1 and mammalian cell migration is directly regulated by Gα and Gα proteins.
J Biol Chem. 2019 Jan 11;294(2):531-546. doi: 10.1074/jbc.RA118.006254. Epub 2018 Nov 16.
4
Distinct Signaling Patterns of Allosteric Antagonism at the P2Y Receptor.
Mol Pharmacol. 2017 Nov;92(5):613-626. doi: 10.1124/mol.117.109660. Epub 2017 Sep 1.
5
RGS14 regulates the lifetime of G-GTP signaling but does not prolong G signaling following receptor activation in live cells.
Pharmacol Res Perspect. 2016 Aug 18;4(5):e00249. doi: 10.1002/prp2.249. eCollection 2016 Oct.
6
Stable G protein-effector complexes in striatal neurons: mechanism of assembly and role in neurotransmitter signaling.
Elife. 2015 Nov 27;4:e10451. doi: 10.7554/eLife.10451.
本文引用的文献
1
G Protein-coupled receptors: Multi-turnover GDP/GTP exchange catalysis on heterotrimeric G proteins.
Cell Logist. 2014 Jun 4;4:e29391. doi: 10.4161/cl.29391. eCollection 2014.
2
A historical perspective on the lateral diffusion model of GTPase activation and related coupling of membrane signaling proteins.
Cell Logist. 2014 Jun 4;4:e29389. doi: 10.4161/cl.29389. eCollection 2014.
3
G protein-coupled receptor oligomerization revisited: functional and pharmacological perspectives.
Pharmacol Rev. 2014 Feb 10;66(2):413-34. doi: 10.1124/pr.113.008052. Print 2014.
4
Activators of G protein signaling exhibit broad functionality and define a distinct core signaling triad.
Mol Pharmacol. 2014 Mar;85(3):388-96. doi: 10.1124/mol.113.090068. Epub 2013 Dec 3.
5
Assembly and function of the regulator of G protein signaling 14 (RGS14)·H-Ras signaling complex in live cells are regulated by Gαi1 and Gαi-linked G protein-coupled receptors.
J Biol Chem. 2013 Feb 1;288(5):3620-31. doi: 10.1074/jbc.M112.440057. Epub 2012 Dec 17.
6
G protein trafficking.
Subcell Biochem. 2012;63:193-223. doi: 10.1007/978-94-007-4765-4_11.
7
G protein-coupled receptors and resistance to inhibitors of cholinesterase-8A (Ric-8A) both regulate the regulator of g protein signaling 14 RGS14·Gαi1 complex in live cells.
J Biol Chem. 2011 Nov 4;286(44):38659-38669. doi: 10.1074/jbc.M111.274928. Epub 2011 Aug 31.
8
Inactive-state preassembly of G(q)-coupled receptors and G(q) heterotrimers.
Nat Chem Biol. 2011 Aug 28;7(10):740-7. doi: 10.1038/nchembio.642.
9
Group II activators of G-protein signalling and proteins containing a G-protein regulatory motif.
Acta Physiol (Oxf). 2012 Feb;204(2):202-18. doi: 10.1111/j.1748-1716.2011.02327.x. Epub 2011 Jul 5.
10
Regulation of the AGS3·G{alpha}i signaling complex by a seven-transmembrane span receptor.
J Biol Chem. 2010 Oct 29;285(44):33949-58. doi: 10.1074/jbc.M110.138073. Epub 2010 Aug 17.
Zotero 插件