G-protein-coupled receptors, channels, and Na+–H+ exchanger in nuclear membranes of heart, hepatic, vascular endothelial, and smooth muscle cellsThis 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. 431-441 ◽  
Author(s):  
Ghassan Bkaily ◽  
Moni Nader ◽  
Levon Avedanian ◽  
Sana Choufani ◽  
Danielle Jacques ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
G Protein ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Specific Cell ◽  
Endothelin 1 ◽  
Nuclear Membranes ◽  
Ionic Transporters ◽  
A Cell ◽  
G Protein Coupled

The action of several peptides and drugs is thought to be primarily dependent on their interactions with specific cell surface G-protein-coupled receptors and ionic transporters such as channels and exchangers. Recent development of 3-D confocal microscopy allowed several laboratories, including ours, to identify and study the localization of receptors, channels, and exchangers at the transcellular level of several cell types. Using this technique, we demonstrated in the nuclei of several types of cells the presence of Ca2+ channels as well as Na+–H+ exchanger and receptors such as endothelin-1 and angiotensin II receptors. Stimulation of these nuclear membrane G-protein-coupled receptors induced an increase of nuclear Ca2+. Our results suggest that, similar to the plasma membrane, nuclear membranes possess channels, exchangers and receptors such as those for endothelin-1 and angiotensin II, and that the nucleus seems to be a cell within a cell. This article will emphasize these findings.

scholarly journals Lysophospholipids in the limelight

2002 ◽  
Vol 158 (2) ◽  
pp. 197-199 ◽  
Author(s):  
Wouter H. Moolenaar
Keyword(s):  
Growth Factor ◽  
Cell Motility ◽  
Tumor Progression ◽  
G Protein ◽  
Lysophosphatidic Acid ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Serum Phospholipid ◽  
A Cell ◽  
G Protein Coupled

Lysophosphatidic acid (LPA) is a serum phospholipid that evokes growth factor–like responses in many cell types through the activation of its G protein–coupled receptors. Although much is known about LPA signaling, it has remained unclear where and how bioactive LPA is produced. Umezu-Goto et al. (2002)(this issue, page 227) have purified a serum lysophospholipase D that generates LPA from lysophosphatidylcholine and found it to be identical to autotaxin, a cell motility–stimulating ectophosphodiesterase implicated in tumor progression. This result is surprising, as there was previously no indication that autotaxin could act as a phospholipase.

scholarly journals Proton-sensing G protein-coupled receptors: detectors of tumor acidosis and candidate drug targets

2020 ◽  
Vol 12 (6) ◽  
pp. 523-532 ◽  
Author(s):  
Paul A Insel ◽  
Krishna Sriram ◽  
Cristina Salmerón ◽  
Shu Z Wiley
Keyword(s):  
G Protein ◽  
Drug Targets ◽  
Tumor Biology ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Specific Cell ◽  
Tumor Microenvironments ◽  
Candidate Drug ◽  
Survival And Growth ◽  
G Protein Coupled

Cells in tumor microenvironments (TMEs) use several mechanisms to sense their low pH (<7.0), including via proton-sensing G protein-coupled receptors (psGPCRs): GPR4, GPR65/TDAG8, GPR68/OGR1 and GPR132/G2A. Numerous cancers have increased expression of psGPCRs. The psGPCRs may contribute to features of the malignant phenotype via actions on specific cell-types in the TME and thereby promote tumor survival and growth. Here, we review data regarding psGPCR expression in tumors and cancer cells, impact of psGPCRs on survival in solid tumors and a bioinformatics approach to infer psGPCR expression in cell types in the TME. New tools are needed to help define contributions of psGPCRs in tumor biology and to identify potentially novel therapeutic agents for a variety of cancers.

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.

Selective recruitment of arrestin-3 to clathrin coated pits upon stimulation of G protein-coupled receptors

2000 ◽  
Vol 113 (13) ◽  
pp. 2463-2470 ◽  
Author(s):  
F. Santini ◽  
R.B. Penn ◽  
A.W. Gagnon ◽  
J.L. Benovic ◽  
J.H. Keen
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Coated Pits ◽  
Over Expression ◽  
Physiological Conditions ◽  
A Cell ◽  
G Protein Coupled ◽  
Comparable Magnitude

Non-visual arrestins (arrestin-2 and arrestin-3) play critical roles in the desensitization and internalization of many G protein-coupled receptors. In vitro experiments have shown that both non-visual arrestins bind with high and approximately comparable affinities to activated, phosphorylated forms of receptors. They also exhibit high affinity binding, again of comparable magnitude, to clathrin. Further, agonist-promoted internalization of many receptors has been found to be stimulated by exogenous over-expression of either arrestin2 or arrestin3. The existence of multiple arrestins raises the question whether stimulated receptors are selective for a specific endogenous arrestin under more physiological conditions. Here we address this question in RBL-2H3 cells, a cell line that expresses comparable levels of endogenous arrestin-2 and arrestin-3. When (beta)(2)-adrenergic receptors are stably expressed in these cells the receptors internalize efficiently following agonist stimulation. However, by immunofluorescence microscopy we determine that only arrestin-3, but not arrestin-2, is rapidly recruited to clathrin coated pits upon receptor stimulation. Similarly, in RBL-2H3 cells that stably express physiological levels of m1AChR, the addition of carbachol selectively induces the localization of arrestin-3, but not arrestin-2, to coated pits. Thus, this work demonstrates coupling of G protein-coupled receptors to a specific non-visual arrestin in an in vivo setting.

scholarly journals A Minimal Model for G Protein–Mediated Synaptic Facilitation and Depression

2003 ◽  
Vol 90 (3) ◽  
pp. 1643-1653 ◽  
Author(s):  
Richard Bertram ◽  
Jessica Swanson ◽  
Mohammad Yousef ◽  
Zhong-Ping Feng ◽  
Gerald W. Zamponi
Keyword(s):  
G Protein ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Β Subunit ◽  
Short Term ◽  
Paired Pulse ◽  
Synaptic Facilitation ◽  
Protein Inhibition ◽  
G Protein Coupled ◽  
High Pass

G protein–coupled receptors are ubiquitous in neurons, as well as other cell types. Activation of receptors by hormones or neurotransmitters splits the G protein heterotrimer into Gα and Gβγ subunits. It is now clear that Gβγ directly inhibits Ca2+ channels, putting them into a reluctant state. The effects of Gβγ depend on the specific β and γ subunits present, as well as the β subunit isoform of the N-type Ca2+ channel. We describe a minimal mathematical model for the effects of G protein action on the dynamics of synaptic transmission. The model is calibrated by data obtained by transfecting G protein and Ca2+ channel subunits into tsA-201 cells. We demonstrate with numerical simulations that G protein action can provide a mechanism for either short-term synaptic facilitation or depression, depending on the manner in which G protein–coupled receptors are activated. The G protein action performs high-pass filtering of the presynaptic signal, with a filter cutoff that depends on the combination of G protein and Ca2+ channel subunits present. At stimulus frequencies above the cutoff, trains of single spikes are transmitted, while only doublets are transmitted at frequencies below the cutoff. Finally, we demonstrate that relief of G protein inhibition can contribute to paired-pulse facilitation.

scholarly journals Chemogenetic Tools for Causal Cellular and Neuronal Biology

2018 ◽  
Vol 98 (1) ◽  
pp. 391-418 ◽  
Author(s):  
Deniz Atasoy ◽  
Scott M. Sternson
Keyword(s):  
G Protein ◽  
Ex Vivo ◽  
Cell Types ◽  
Cell Populations ◽  
Specific Cell ◽  
Cellular Processes ◽  
Distinct Cell ◽  
G Protein Coupled ◽  
Pharmacological Control

Chemogenetic technologies enable selective pharmacological control of specific cell populations. An increasing number of approaches have been developed that modulate different signaling pathways. Selective pharmacological control over G protein-coupled receptor signaling, ion channel conductances, protein association, protein stability, and small molecule targeting allows modulation of cellular processes in distinct cell types. Here, we review these chemogenetic technologies and instances of their applications in complex tissues in vivo and ex vivo.

Intracrine signaling through lipid mediators and their cognate nuclear G-protein-coupled receptors: a paradigm based on PGE2, PAF, and LPA1 receptorsThis 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. 377-391 ◽  
Author(s):  
Tang Zhu ◽  
Fernand Gobeil ◽  
Alejandro Vazquez-Tello ◽  
Martin Leduc ◽  
Lenka Rihakova ◽  
...  
Keyword(s):  
G Protein ◽  
Nuclear Localization ◽  
Platelet Activating Factor ◽  
Rat Hepatocytes ◽  
Lipid Mediators ◽  
G Protein Coupled Receptors ◽  
Membrane Receptors ◽  
Surface Receptors ◽  
A Cell ◽  
G Protein Coupled

Prostaglandins (PGs), platelet-activating factor (PAF), and lysophosphatidic acid (LPA) are ubiquitous lipid mediators that play important roles in inflammation, cardiovascular homeostasis, and immunity and are also known to modulate gene expression of specific pro-inflammatory genes. The mechanism of action of these lipids is thought to be primarily dependent on their specific plasma membrane receptors belonging to the superfamily of G-protein-coupled receptors (GPCR). Increasing evidence suggests the existence of a functional intracellular GPCR population. It has been proposed that immediate effects are mediated via cell surface receptors whereas long-term responses are dependent upon intracellular receptor effects. Indeed, receptors for PAF, LPA, and PGE2 (specifically EP1, EP3, and EP4) localize at the cell nucleus of cerebral microvascular endothelial cells of newborn pigs, rat hepatocytes, and cells overexpressing each receptor. Stimulation of isolated nuclei with these lipids reveals biological functions including transcriptional regulation of major genes, namely c-fos, cylooxygenase-2, and endothelial as well as inducible nitric oxide synthase. In the present review, we shall focus on the nuclear localization and signaling of GPCRs recognizing PGE2, PAF, and LPA phospholipids as ligands. Mechanisms on how nuclear PGE2, PAF, and LPA receptors activate gene transcription and nuclear localization pathways are presented. Intracrine signaling for lipid mediators uncover novel pathways to elicit their effects; accordingly, intracellular GPCRs constitute a distinctive mode of action for gene regulation.

Expression of G protein coupled receptors in a cell-free translational system using detergents and thioredoxin-fusion vectors

2005 ◽  
Vol 41 (1) ◽  
pp. 27-37 ◽  
Author(s):  
Goshi Ishihara ◽  
Mie Goto ◽  
Mihoro Saeki ◽  
Kaori Ito ◽  
Tetsuya Hori ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
A Cell ◽  
G Protein Coupled

scholarly journals Roles of G Protein-Coupled Receptors (GPCRs) in Gastrointestinal Cancers: Focus on Sphingosine 1-Shosphate Receptors, Angiotensin II Receptors, and Estrogen-Related GPCRs

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2988
Author(s):  
Zhen Zeng ◽  
Chunxiang Ma ◽  
Kexin Chen ◽  
Mingshan Jiang ◽  
Reshma Vasu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Angiotensin Ii Receptors ◽  
Biological Processes ◽  
Substantial Evidence ◽  
Sphingosine 1 Phosphate ◽  
Gi Cancers ◽  
G Protein Coupled ◽  
Made In

It is well established that gastrointestinal (GI) cancers are common and devastating diseases around the world. Despite the significant progress that has been made in the treatment of GI cancers, the mortality rates remain high, indicating a real need to explore the complex pathogenesis and develop more effective therapeutics for GI cancers. G protein-coupled receptors (GPCRs) are critical signaling molecules involved in various biological processes including cell growth, proliferation, and death, as well as immune responses and inflammation regulation. Substantial evidence has demonstrated crucial roles of GPCRs in the development of GI cancers, which provided an impetus for further research regarding the pathophysiological mechanisms and drug discovery of GI cancers. In this review, we mainly discuss the roles of sphingosine 1-phosphate receptors (S1PRs), angiotensin II receptors, estrogen-related GPCRs, and some other important GPCRs in the development of colorectal, gastric, and esophageal cancer, and explore the potential of GPCRs as therapeutic targets.

scholarly journals Chemogenetic activation of astrocytes in the hippocampus and cortex changes the transcriptome of microglia and other cell types

2020 ◽  
Author(s):  
Stéphanie Philtjens ◽  
Marion T. Turnbull ◽  
Brian P. Thedy ◽  
Younghye Moon ◽  
Jungsu Kim
Keyword(s):  
Single Cell ◽  
G Protein ◽  
Low Density Lipoprotein ◽  
Ion Homeostasis ◽  
Density Lipoprotein ◽  
Cell Types ◽  
Designer Drugs ◽  
Specific Cell ◽  
G Protein Coupled

AbstractAstrocytes are the most common glial cell type in the brain, yet, it is still not clear how their activation affects the transcriptome of other brain cells such as microglia and neurons. Engineered G protein-coupled receptors called Designer Receptors Exclusively Activated by Designer Drugs (DREADDS) make it possible to selectively activate specific cell types, such as neurons and astrocytes. By combining the selective activation of astrocytes with single cell RNA sequencing, we were able to study transcriptional changes that occur in response to the activation of astrocytes at the single cell level. Interestingly, our data shows that long-term activation of astrocytes in healthy mice results in dramatic alteration in the transcriptome of astrocytes and microglia. Genes that were differentially expressed in these Gq-DREADD-activated astrocytes were involved in neurogenesis and low density lipoprotein particle biology, while those in the microglia were involved in the response to lipoproteins, and the migration and chemotaxis of immune cells. Furthermore, network analysis showed that Gq-DREADD-mediated activation in astrocytes resulted in an upregulation of genes involved in the G protein-coupled receptor signaling pathway and calcium ion homeostasis. This confirmed the activation of astrocytes through the expressed DREADDS. Our findings show the importance of considering the transcriptomic alteration in microglia and neurons after the activation of astrocytes in in vivo models. Therefore, our data will serve as a resource for the broader neuroscience community.

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