Emerging Role of Compartmentalized G Protein-Coupled Receptor Signaling in the Cardiovascular Field

被引:35
作者
Plouffe, Bianca [1 ]
Thomsen, Alex R. B. [2 ]
Irannejad, Roshanak [3 ]
机构
[1] Queens Univ Belfast, Wellcome Wolfson Inst Expt Med, Belfast BT9 7BL, Antrim, North Ireland
[2] NYU, Coll Dent, Dept Basic Sci & Craniofacial Biol, New York, NY 10010 USA
[3] Univ Calif San Francisco, Dept Biochem & Biophys, Cardiovasc Res Inst, San Francisco, CA 94158 USA
基金
英国惠康基金;
关键词
compartmentalized G protein signaling; sustained signaling; early endosomes; Golgi membranes; nuclear membranes; heart failure (HF); atherosclerosis; myocardial ischemia; cardioprotection; beta-adrenergic receptors (beta ARs); vasopressin type 2 receptor (V2R); calcitonin gene-related peptide (CGRP) receptor; US28; sphingosine-1-phosphate 1 receptor (S1P(1)R); GENE-RELATED PEPTIDE; HUMAN CYTOMEGALOVIRUS US28; CIRCULATING MATURE LYMPHOCYTES; ISCHEMIA-REPERFUSION INJURY; BETA-ARRESTIN COMPLEXES; CHRONIC HEART-FAILURE; CALCITONIN-GENE; SPHINGOSINE; 1-PHOSPHATE; BETA(2)-ADRENERGIC RECEPTOR; BETA-2-ADRENERGIC RECEPTOR;
D O I
10.1021/acsptsci.0c00006
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
G protein-coupled receptors (GPCRs) are cell surface receptors that for many years have been considered to function exclusively at the plasma membrane, where they bind to extracellular ligands and activate G protein signaling cascades. According to the conventional model, these signaling events are rapidly terminated by beta-arrestin (beta-arr) recruitment to the activated GPCR resulting in signal desensitization and receptor internalization. However, during the past decade, emerging evidence suggest that many GPCRs can continue to activate G proteins from intracellular compartments after they have been internalized. G protein signaling from intracellular compartments is in general more sustained compared to G protein signaling at the plasma membrane. Notably, the particular location closer to the nucleus is beneficial for selective cellular functions such as regulation of gene transcription. Here, we review key GPCRs that undergo compartmentalized G protein signaling and discuss molecular considerations and requirements for this signaling to occur. Our main focus will be on receptors involved in the regulation of important physiological and pathological cardiovascular functions. We also discuss how sustained G protein activation from intracellular compartments may be involved in cellular functions that are distinct from functions regulated by plasma membrane G protein signaling, and the corresponding significance in cardiovascular physiology.
引用
收藏
页码:221 / 236
页数:16
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