scholarly journals Chemotactic Ligands that Activate G-Protein-Coupled Formylpeptide Receptors

2019 ◽  
Vol 20 (14) ◽  
pp. 3426 ◽  
Author(s):  
Stacey A Krepel ◽  
Ji Ming Wang
Keyword(s):  
G Protein ◽  
Cancer Progression ◽  
Inflammatory Responses ◽  
Myeloid Cell ◽  
Cell Types ◽  
Cell Trafficking ◽  
Microbial Infection ◽  
Physiological Processes ◽  
Recent Developments ◽  
G Protein Coupled

Leukocyte infiltration is a hallmark of inflammatory responses. This process depends on the bacterial and host tissue-derived chemotactic factors interacting with G-protein-coupled seven-transmembrane receptors (GPCRs) expressed on the cell surface. Formylpeptide receptors (FPRs in human and Fprs in mice) belong to the family of chemoattractant GPCRs that are critical mediators of myeloid cell trafficking in microbial infection, inflammation, immune responses and cancer progression. Both murine Fprs and human FPRs participate in many patho-physiological processes due to their expression on a variety of cell types in addition to myeloid cells. FPR contribution to numerous pathologies is in part due to its capacity to interact with a plethora of structurally diverse chemotactic ligands. One of the murine Fpr members, Fpr2, and its endogenous agonist peptide, Cathelicidin-related antimicrobial peptide (CRAMP), control normal mouse colon epithelial growth, repair and protection against inflammation-associated tumorigenesis. Recent developments in FPR (Fpr) and ligand studies have greatly expanded the scope of these receptors and ligands in host homeostasis and disease conditions, therefore helping to establish these molecules as potential targets for therapeutic intervention.

Lysophosphatidylinositol: a novel link between ABC transporters and G-protein-coupled receptors

2014 ◽  
Vol 42 (5) ◽  
pp. 1372-1377 ◽  
Author(s):  
Emily L. Ruban ◽  
Riccardo Ferro ◽  
Syamsul Ahmad Arifin ◽  
Marco Falasca
Keyword(s):  
Cell Proliferation ◽  
G Protein ◽  
Cancer Progression ◽  
Multidrug Resistance Protein 1 ◽  
Autocrine Loop ◽  
Cell Functions ◽  
Cytosolic Phospholipase ◽  
Signalling Cascades ◽  
Novel Strategy ◽  
G Protein Coupled

Lysophosphatidylinositol (LPI) is a well-known bioactive lipid that is able to activate signalling cascades relevant to cell proliferation, migration, survival and tumorigenesis. Our previous work suggested that LPI is involved in cancer progression since it can be released in the medium of Ras-transformed fibroblasts and can function as an autocrine modulator of cell growth. Different research groups have established that LPI is the specific and functional ligand for G-protein-coupled receptor 55 (GPR55) and that this GPR55–LPI axis is able to activate signalling cascades that are relevant for different cell functions. Work in our laboratory has recently unravelled an autocrine loop, by which LPI synthesized by cytosolic phospholipase A2 (cPLA2) is pumped out of the cell by ATP-binding cassette (ABC) transporter C1 (ABCC1)/multidrug resistance protein 1 (MRP1), initiating a signalling cascade downstream of GPR55. Our current work suggests that blockade of this pathway may represent a novel strategy to inhibit cancer cell proliferation.

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.

Compartmentalization of GPCR signalling controls unique cellular responses

2016 ◽  
Vol 44 (2) ◽  
pp. 562-567 ◽  
Author(s):  
Andrew M. Ellisdon ◽  
Michelle L. Halls
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Attrition Rates ◽  
Physiological Processes ◽  
Simple Chain ◽  
G Protein Coupled ◽  
Major Drug ◽  
Very High

With >800 members, G protein-coupled receptors (GPCRs) are the largest class of cell-surface signalling proteins, and their activation mediates diverse physiological processes. GPCRs are ubiquitously distributed across all cell types, involved in many diseases and are major drug targets. However, GPCR drug discovery is still characterized by very high attrition rates. New avenues for GPCR drug discovery may be provided by a recent shift away from the traditional view of signal transduction as a simple chain of events initiated from the plasma membrane. It is now apparent that GPCR signalling is restricted to highly organized compartments within the cell, and that GPCRs activate distinct signalling pathways once internalized. A high-resolution understanding of how compartmentalized signalling is controlled will probably provide unique opportunities to selectively and therapeutically target GPCRs.

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.

scholarly journals Out-of-the-groove transport of lipids by TMEM16 and GPCR scramblases

2018 ◽  
Vol 115 (30) ◽  
pp. E7033-E7042 ◽  
Author(s):  
Mattia Malvezzi ◽  
Kiran K. Andra ◽  
Kalpana Pandey ◽  
Byoung-Cheol Lee ◽  
Maria E. Falzone ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
G Protein ◽  
Credit Card ◽  
Protein Families ◽  
G Protein Coupled Receptor ◽  
Physiological Processes ◽  
Phospholipid Scrambling ◽  
Conformational Rearrangements ◽  
G Protein Coupled ◽  
Gpcr Protein

Phospholipid scramblases externalize phosphatidylserine to facilitate numerous physiological processes. Several members of the structurally unrelated TMEM16 and G protein-coupled receptor (GPCR) protein families mediate phospholipid scrambling. The structure of a TMEM16 scramblase shows a membrane-exposed hydrophilic cavity, suggesting that scrambling occurs via the ‟credit-card” mechanism where lipid headgroups permeate through the cavity while their tails remain associated with the membrane core. Here we show that afTMEM16 and opsin, representatives of the TMEM16 and GCPR scramblase families, transport phospholipids with polyethylene glycol headgroups whose globular dimensions are much larger than the width of the cavity. This suggests that transport of these large headgroups occurs outside rather than within the cavity. These large lipids are scrambled at rates comparable to those of normal phospholipids and their presence in the reconstituted vesicles promotes scrambling of normal phospholipids. This suggests that both large and small phospholipids can move outside the cavity. We propose that the conformational rearrangements underlying TMEM16- and GPCR-mediated credit-card scrambling locally deform the membrane to allow transbilayer lipid translocation outside the cavity and that both mechanisms underlie transport of normal phospholipids.

Identification Methods of G Protein-Coupled Receptors

2011 ◽  
Vol 2 (4) ◽  
pp. 35-52
Author(s):  
Meriem Zekri ◽  
Karima Alem ◽  
Labiba Souici-Meslati
Keyword(s):  
Immune Responses ◽  
G Protein ◽  
Pharmaceutical Research ◽  
G Protein Coupled Receptors ◽  
Machine Learning Algorithms ◽  
Signaling Networks ◽  
Identification Methods ◽  
Physiological Processes ◽  
Cell Signaling Networks ◽  
G Protein Coupled

The G protein-coupled receptors (GPCRs) include one of the largest and most important families of multifunctional proteins known to molecular biology. They play a key role in cell signaling networks that regulate many physiological processes, such as vision, smell, taste, neurotransmission, secretion, immune responses, metabolism, and cell growth. These proteins are thus very important for understanding human physiology and they are involved in several diseases. Therefore, many efforts in pharmaceutical research are to understand their structures and functions, which is not an easy task, because although thousands GPCR sequences are known, many of them remain orphans. To remedy this, many methods have been developed using methods such as statistics, machine learning algorithms, and bio-inspired approaches. In this article, the authors review the approaches used to develop algorithms for classification GPCRs by trying to highlight the strengths and weaknesses of these different approaches and providing a comparison of their performances.

scholarly journals G-Protein-Coupled Estrogen Receptor (GPER)-Specific Agonist G1 Induces ER Stress Leading to Cell Death in MCF-7 Cells

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 503 ◽  
Author(s):  
Diep-Khanh Ho Vo ◽  
Roland Hartig ◽  
Sönke Weinert ◽  
Johannes Haybaeck ◽  
Norbert Nass
Keyword(s):  
Cell Death ◽  
Estrogen Receptor ◽  
Er Stress ◽  
G Protein ◽  
Cancer Progression ◽  
Cancer Cell Line ◽  
Positive Breast Cancer Cell ◽  
The Unfolded Protein Response ◽  
G Protein Coupled ◽  
Mcf 7

The G-protein-coupled estrogen receptor (GPER) mediates rapid non-genomic effects of estrogen. Although GPER is able to induce proliferation, it is down-regulated in breast, ovarian and colorectal cancer. During cancer progression, high expression levels of GPER are favorable for patients’ survival. The GPER-specific agonist G1 leads to an inhibition of cell proliferation and an elevated level of intracellular calcium (Ca2+). The purpose of this study is to elucidate the mechanism of G1-induced cell death by focusing on the connection between G1-induced Ca2+ depletion and endoplasmic reticulum (ER) stress in the estrogen receptor positive breast cancer cell line MCF-7. We found that G1-induced ER Ca2+ efflux led to the activation of the unfolded protein response (UPR), indicated by the phosphorylation of IRE1α and PERK and the cleavage of ATF6. The pro-survival UPR signaling was activated via up-regulation of the ER chaperon protein GRP78 and translational attenuation indicated by eIF2-α phosphorylation. However, the accompanying pro-death UPR signaling is profoundly activated and responsible for ER stress-induced cell death. Mechanistically, PERK-phosphorylation-induced JNK-phosphorylation and IRE1α-phosphorylation, which further triggered CAMKII-phosphorylation, are both implicated in G1-induced cell death. Our study indicates that loss of ER Ca2+ is responsible for G1-induced cell death via the pro-death UPR signaling.

scholarly journals Characterization and Expression Profiling of Neuropeptides and G-Protein-Coupled Receptors (GPCRs) for Neuropeptides in the Asian Citrus Psyllid, Diaphorina citri (Hemiptera: Psyllidae)

2018 ◽  
Vol 19 (12) ◽  
pp. 3912 ◽  
Author(s):  
Zhengbing Wang ◽  
Wenwu Zhou ◽  
Muhammad Hameed ◽  
Jiali Liu ◽  
Xinnian Zeng
Keyword(s):  
G Protein ◽  
Developmental Stages ◽  
G Protein Coupled Receptors ◽  
Nerve Tissue ◽  
Asian Citrus Psyllid ◽  
Diaphorina Citri ◽  
Physiological Processes ◽  
Neuropeptide Receptors ◽  
G Protein Coupled ◽  
Active Substances

Neuropeptides are endogenous active substances that widely exist in multicellular biological nerve tissue and participate in the function of the nervous system, and most of them act on neuropeptide receptors. In insects, neuropeptides and their receptors play important roles in controlling a multitude of physiological processes. In this project, we sequenced the transcriptome from twelve tissues of the Asian citrus psyllid, Diaphorina citri Kuwayama. A total of 40 candidate neuropeptide genes and 42 neuropeptide receptor genes were identified. Among the neuropeptide receptor genes, 35 of them belong to the A-family (or rhodopsin-like), four of them belong to the B-family (or secretin-like), and three of them are leucine-rich repeat-containing G-protein-coupled receptors. The expression profile of the 82 genes across developmental stages was determined by qRT-PCR. Our study provides the first investigation on the genes of neuropeptides and their receptors in D. citri, which may play key roles in regulating the physiology and behaviors of D. citri.

The calcium-sensing receptor as a nutrient sensor

2005 ◽  
Vol 33 (1) ◽  
pp. 316-320 ◽  
Author(s):  
D. Riccardi ◽  
D. Maldonado-Perez
Keyword(s):  
G Protein ◽  
Cell Fate ◽  
Aromatic Amino Acids ◽  
Cell Types ◽  
Extracellular Calcium ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Sense And Respond ◽  
Acute Changes ◽  
G Protein Coupled

Critical to cell fate in many cell types is the ability to sense and respond to acute changes in free ionized extracellular calcium concentration ([Ca2+]o). Such tight control is mediated by the activation of a protein known as the extracellular-calcium-sensing receptor (CaR). CaR belongs to the ‘family C’ of G-protein-coupled receptors and was the first G-protein-coupled receptor to be identified to have an inorganic cation, calcium, as its ligand. While calcium is the physiological agonist of the receptor, several other polyvalent cations and polycations can also modulate CaR function as do certain L-aromatic amino acids, polyamines, salinity and pH. This feature renders the CaR uniquely capable of generating cell- and tissue-specific responses, and of integrating inputs deriving from changes in the Ca2+o concentration with signals deriving from the local metabolic environment. Here we address the role of the CaR in physiology and disease, the range of CaR modulators and the potential roles of the CaR as a metabolic sensor in a variety of physiological (and pathological) scenarios.

scholarly journals The Prokineticins: Neuromodulators and Mediators of Inflammation and Myeloid Cell-Dependent Angiogenesis

2018 ◽  
Vol 98 (2) ◽  
pp. 1055-1082 ◽  
Author(s):  
Lucia Negri ◽  
Napoleone Ferrara
Keyword(s):  
Cancer Progression ◽  
Developmental Disorder ◽  
Tissue Injury ◽  
Myeloid Cell ◽  
Inflammatory Cells ◽  
G Protein Coupled Receptors ◽  
Mediators Of Inflammation ◽  
Motility Regulation ◽  
G Protein Coupled ◽  
Stimulating Factor

The mammalian prokineticins family comprises two conserved proteins, EG-VEGF/PROK1 and Bv8/PROK2, and their two highly related G protein-coupled receptors, PKR1 and PKR2. This signaling system has been linked to several important biological functions, including gastrointestinal tract motility, regulation of circadian rhythms, neurogenesis, angiogenesis and cancer progression, hematopoiesis, and nociception. Mutations in PKR2 or Bv8/PROK2 have been associated with Kallmann syndrome, a developmental disorder characterized by defective olfactory bulb neurogenesis, impaired development of gonadotropin-releasing hormone neurons, and infertility. Also, Bv8/PROK2 is strongly upregulated in neutrophils and other inflammatory cells in response to granulocyte-colony stimulating factor or other myeloid growth factors and functions as a pronociceptive mediator in inflamed tissues as well as a regulator of myeloid cell-dependent tumor angiogenesis. Bv8/PROK2 has been also implicated in neuropathic pain. Anti-Bv8/PROK2 antibodies or small molecule PKR inhibitors ameliorate pain arising from tissue injury and inhibit angiogenesis and inflammation associated with tumors or some autoimmune disorders.

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