Regulation of G protein-coupled receptor endocytosis by ARF6 GTP-binding proteins

2004 ◽  
Vol 82 (6) ◽  
pp. 610-617 ◽  
Author(s):  
Audrey Claing
Keyword(s):  
G Protein ◽  
Molecular Mechanisms ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled Receptor ◽  
Adp Ribosylation ◽  
Internalization Process ◽  
Intracellular Compartments ◽  
Broad Variety ◽  
Membrane Bound ◽  
G Protein Coupled

The function of G protein-coupled receptors is regulated by a broad variety of membrane-bound and intracellular proteins. These act in concert to activate signaling pathways that will lead to the desensitization of activated receptors and, for most receptor types, their trafficking to intracellular compartments. This review focuses mainly on the endocytic pathways used by a G protein-coupled receptor and on the proteins that play an essential role in the regulation of the internalization process, most specifically the ADP-ribosylation factors. This family of proteins has been shown to be important for vesicle trafficking between different cellular membranes. The latest findings regarding the molecular mechanisms that regulate internalization of an agonist-stimulated receptor are presented here. Finally, a perspective on how ARF6 proteins might regulate the internalization process is also proposed.Key words: G protein-coupled receptors, endocytosis, ADP-ribosylation factor.

G-protein-coupled receptors signalling at the cell nucleus: an emerging paradigmThis paper is one of a selection of papers published in this Special Issue, entitled The Nucleus: A Cell Within A Cell.

2006 ◽  
Vol 84 (3-4) ◽  
pp. 287-297 ◽  
Author(s):  
Fernand Gobeil ◽  
Audrey Fortier ◽  
Tang Zhu ◽  
Michela Bossolasco ◽  
Martin Leduc ◽  
...  
Keyword(s):  
G Protein ◽  
Cell Nucleus ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Cell Metabolism ◽  
Hormone Secretion ◽  
G Protein Coupled Receptors ◽  
A Cell ◽  
G Protein Coupled

G-protein-coupled receptors (GPCRs) comprise a wide family of monomeric heptahelical glycoproteins that recognize a broad array of extracellular mediators including cationic amines, lipids, peptides, proteins, and sensory agents. Thus far, much attention has been given towards the comprehension of intracellular signaling mechanisms activated by cell membrane GPCRs, which convert extracellular hormonal stimuli into acute, non-genomic (e.g., hormone secretion, muscle contraction, and cell metabolism) and delayed, genomic biological responses (e.g., cell division, proliferation, and apoptosis). However, with respect to the latter response, there is compelling evidence for a novel intracrine mode of genomic regulation by GPCRs that implies either the endocytosis and nuclear translocation of peripheral-liganded GPCR and (or) the activation of nuclearly located GPCR by endogenously produced, nonsecreted ligands. A noteworthy example of the last scenario is given by heptahelical receptors that are activated by bioactive lipoids (e.g., PGE2 and PAF), many of which may be formed from bilayer membranes including those of the nucleus. The experimental evidence for the nuclear localization and signalling of GPCRs will be reviewed. We will also discuss possible molecular mechanisms responsible for the atypical compartmentalization of GPCRs at the cell nucleus, along with their role in gene expression.

scholarly journals Ionotropic and Metabotropic Proton-Sensing Receptors Involved in Airway Inflammation in Allergic Asthma

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Haruka Aoki ◽  
Chihiro Mogi ◽  
Fumikazu Okajima
Keyword(s):  
Airway Inflammation ◽  
Allergic Asthma ◽  
G Protein ◽  
Molecular Mechanisms ◽  
G Protein Coupled Receptors ◽  
Airway Smooth Muscle Cells ◽  
Transient Receptor Potential Vanilloid ◽  
Acidic Ph ◽  
Airway Responses ◽  
G Protein Coupled

An acidic microenvironment has been shown to evoke a variety of airway responses, including cough, bronchoconstriction, airway hyperresponsiveness (AHR), infiltration of inflammatory cells in the lung, and stimulation of mucus hyperproduction. Except for the participation of transient receptor potential vanilloid-1 (TRPV1) and acid-sensing ion channels (ASICs) in severe acidic pH (of less than 6.0)-induced cough and bronchoconstriction through sensory neurons, the molecular mechanisms underlying extracellular acidic pH-induced actions in the airways have not been fully understood. Recent studies have revealed that ovarian cancer G protein-coupled receptor 1 (OGR1)-family G protein-coupled receptors, which sense pH of more than 6.0, are expressed in structural cells, such as airway smooth muscle cells and epithelial cells, and in inflammatory and immune cells, such as eosinophils and dendritic cells. They function in a variety of airway responses related to the pathophysiology of inflammatory diseases, including allergic asthma. In the present review, we discuss the roles of ionotropic TRPV1 and ASICs and metabotropic OGR1-family G protein-coupled receptors in the airway inflammation and AHR in asthma and respiratory diseases.

scholarly journals Misfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects

2021 ◽  
Vol 22 (22) ◽  
pp. 12329
Author(s):  
Alfredo Ulloa-Aguirre ◽  
Teresa Zariñán ◽  
Eduardo Jardón-Valadez
Keyword(s):  
Plasma Membrane ◽  
G Protein ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
G Protein Coupled Receptors ◽  
Membrane Receptors ◽  
Therapeutic Interventions ◽  
Endocrine Function ◽  
Receptor Protein ◽  
G Protein Coupled

Misfolding of G protein-coupled receptors (GPCRs) caused by mutations frequently leads to disease due to intracellular trapping of the conformationally abnormal receptor. Several endocrine diseases due to inactivating mutations in GPCRs have been described, including X-linked nephrogenic diabetes insipidus, thyroid disorders, familial hypocalciuric hypercalcemia, obesity, familial glucocorticoid deficiency [melanocortin-2 receptor, MC2R (also known as adrenocorticotropin receptor, ACTHR), and reproductive disorders. In these mutant receptors, misfolding leads to endoplasmic reticulum retention, increased intracellular degradation, and deficient trafficking of the abnormal receptor to the cell surface plasma membrane, causing inability of the receptor to interact with agonists and trigger intracellular signaling. In this review, we discuss the mechanisms whereby mutations in GPCRs involved in endocrine function in humans lead to misfolding, decreased plasma membrane expression of the receptor protein, and loss-of-function diseases, and also describe several experimental approaches employed to rescue trafficking and function of the misfolded receptors. Special attention is given to misfolded GPCRs that regulate reproductive function, given the key role played by these particular membrane receptors in sexual development and fertility, and recent reports on promising therapeutic interventions targeting trafficking of these defective proteins to rescue completely or partially their normal function.

scholarly journals G Protein-coupled Receptor Kinases of the GRK4 Protein Subfamily Phosphorylate Inactive G Protein-coupled Receptors (GPCRs)

2015 ◽  
Vol 290 (17) ◽  
pp. 10775-10790 ◽  
Author(s):  
Lingyong Li ◽  
Kristoff T. Homan ◽  
Sergey A. Vishnivetskiy ◽  
Aashish Manglik ◽  
John J. G. Tesmer ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled Receptor ◽  
Receptor Kinases ◽  
G Protein Coupled

scholarly journals ADP-Ribosylation Factors Modulate the Cell Surface Transport of G Protein-Coupled Receptors

2010 ◽  
Vol 333 (1) ◽  
pp. 174-183 ◽  
Author(s):  
Chunmin Dong ◽  
Xiaoping Zhang ◽  
Fuguo Zhou ◽  
Huijuan Dou ◽  
Matthew T. Duvernay ◽  
...  
Keyword(s):  
Cell Surface ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Surface Transport ◽  
Adp Ribosylation ◽  
G Protein Coupled

Molecular mechanisms of G protein-coupled receptor desensitization and resensitization

Life Sciences ◽  
1998 ◽  
Vol 62 (17-18) ◽  
pp. 1561-1565 ◽  
Author(s):  
Stephen S.G. Ferguson ◽  
Jie Zhang ◽  
Larry S. Barakt ◽  
Marc G. Caron
Keyword(s):  
G Protein ◽  
Molecular Mechanisms ◽  
Receptor Desensitization ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled
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