Search results for "GPC"
showing 10 items of 24 documents
Identification of processes that control the stable isotope composition of rainwater in the humid tropical West-Central Africa.
2020
12 pages; International audience; This study interprets 11 years (2006 to 2016) and 6 months (March to August in 2017) of respectively monthly and daily isotopic (δD and δ18O) monitoring of rain at Douala (Cameroon), a humid tropical station in Western Africa. The main scope is to analyze the climate controls on precipitation isotopes at different timescales. Firstly, we examine the annual cycles of δ18O. Over the 11 years of survey, the annual cycle exhibits a W shape that is quite reproducible from year to year, with two minima in spring and autumn periods. Based on back trajectory calculations and remote sensing observations of water vapor isotopic composition, we show that the observed …
NMR Investigation of Structures of G-Protein Coupled Receptor Folding Intermediates
2016
Folding of G-protein coupled receptors (GPCRs) according to the two-stage model (Popot, J. L., and Engelman, D. M. (1990) Biochemistry 29, 4031-4037) is postulated to proceed in 2 steps: partitioning of the polypeptide into the membrane followed by diffusion until native contacts are formed. Herein we investigate conformational preferences of fragments of the yeast Ste2p receptor using NMR. Constructs comprising the first, the first two, and the first three transmembrane (TM) segments, as well as a construct comprising TM1-TM2 covalently linked to TM7 were examined. We observed that the isolated TM1 does not form a stable helix nor does it integrate well into the micelle. TM1 is significant…
An actin network dispatches ciliary GPCRs into extracellular vesicles to modulate signaling
2017
Signaling receptors dynamically exit cilia upon activation of signaling pathways such as Hedgehog. Here, we find that when activated G protein-coupled receptors (GPCRs) fail to undergo BBSome-mediated retrieval from cilia back into the cell, these GPCRs concentrate into membranous buds at the tips of cilia before release into extracellular vesicles named ectosomes. Unexpectedly, actin and the actin regulators drebrin and myosin 6 mediate ectosome release from the tip of cilia. Mirroring signal-dependent retrieval, signal-dependent ectocytosis is a selective and effective process that removes activated signaling molecules from cilia. Congruently, ectocytosis compensates for BBSome defects as…
Crosstalk between receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCR) in the brain: Focus on heteroreceptor complexes and related…
2019
Neuronal events are regulated by the integration of several complex signaling networks in which G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) are considered key players of an intense bidirectional cross-communication in the cell, generating signaling mechanisms that, at the same time, connect and diversify the traditional signal transduction pathways activated by the single receptor. For this receptor-receptor crosstalk, the two classes of receptors form heteroreceptor complexes resulting in RTKs transactivation and in growth-promoting signals. In this review, we describe heteroreceptor complexes between GPCR and RTKs in the central nervous system (CNS) and their …
The Crystal Structure of Gurmarin, a Sweet Taste–Suppressing Protein: Identification of the Amino Acid Residues Essential for Inhibition
2018
International audience; Gurmarin is a highly specific sweet-taste suppressing protein in rodents that is isolated from the Indian plant Gymnemasylvestre. Gurmarin consists of 35 amino acid residues containing three intramolecular disulfide bridges that form a cystine knot. Here, we report the crystal structure of gurmarin at a 1.45 Å resolution and compare it with previously reported NMR solution structures. The atomic structure at this resolution allowed us to identify a very flexible region consisting of hydrophobic residues. Some of these amino acid residues had been identified as a putative binding site for the rat sweet taste receptor in a previous study. By combining alanine-scanning …
Evaluation and comparison of satellite precipitation estimates with reference to a local area in the Mediterranean Sea
2014
Precipitation measurement is a key activity for the analysis of storm processes as well as every hydrological process. Satellite retrieval systems, rain-gauge network and radar systems are complement to each other in terms of their coverage and capability of monitoring precipitation. Satellite rainfall estimates systems produce data with global coverage that can provide information in areas for which data from other sources are unavailable. Without referring to ground measurement, satellite-based estimates can be bias. Although some gauged adjusted satellite precipitation products are developed, an effective way of integrating multi-sources of precipitation information is still a challenge.…
GPCR Inhibition in Treating Lymphoma
2022
G protein-coupled receptors (GPCRs) are important classes of cell surface receptors involved in multiple physiological functions. Aberrant expression, upregulation, and mutation of GPCR signaling pathways are frequent in many types of cancers, promoting hyperproliferation, angiogenesis, and metastasis. Recent studies showed that alterations of GPCRs are involved in different lymphoma types. Herein, we review the synthetic strategies to obtain GPCR inhibitors, focusing on CXCR4 inhibitors which represent most of the GPCR inhibitors available in the market or under preclinical investigations for these diseases.
Metabolite Sensing GPCRs: Promising Therapeutic Targets for Cancer Treatment?
2020
G-protein-coupled receptors constitute the most diverse and largest receptor family in the human genome, with approximately 800 different members identified. Given the well-known metabolic alterations in cancer development, we will focus specifically in the 19 G-protein-coupled receptors (GPCRs), which can be selectively activated by metabolites. These metabolite sensing GPCRs control crucial processes, such as cell proliferation, differentiation, migration, and survival after their activation. In the present review, we will describe the main functions of these metabolite sensing GPCRs and shed light on the benefits of their potential use as possible pharmacological targets for cancer treat…
IDENTIFICATION AND FUNCTIONAL CHARACTERIZATION OF GPCR23/LPA4 AS A CANDIDATE G PROTEIN-COUPLED RECEPTOR FOR GUANOSINE
2014
La guanosina esercita diverse funzioni a livello del Sistema Nervoso Centrale, coinvolgendo recettori di membrana accoppiati a proteine G (GPCR) non ancora identificati. Pertanto, l’obiettivo della ricerca è stato quello di individuare e caratterizzare uno specifico recettore funzionale per la Guanosina. I dati ottenuti su linee cellulari hanno dimostrato che il legame della guanosina con le membrane plasmatiche è incrementato dall’over-espressione del GPCR23 e ridotto dal suo silenziamento ed hanno evidenziato l’attivazione di un GPCR in risposta alla guanosina. A livello cerebrale il GPCR23 è risultato essere maggiormente espresso nella regione corticale, dove si è dimostrata anche una no…
G protein biased signaling by non-catechol dopamine D1 receptor agonists
2020
Dopamine is a catecholamine neurotransmitter with essential roles in voluntary movement, working memory, attention, and reward. Dopamine acts through five G protein coupled receptors with the D1 and D5 receptors (D1R) stimulating Galphas/olf activation and increasing neuronal excitability. Deficits in D1R signaling are implicated in Parkinson’s disease motor deficits as well as cognitive deficits in schizophrenia and attention deficit hyperactivity disorder. For more than 40 years, academic and industry scientists have been searching for a drug-like D1R agonist, but this has remained elusive. The challenge in developing D1R selective agonists is that all previous agonists possess a common p…