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Related Concept Videos

GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

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Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
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G Protein-coupled Receptors01:15

G Protein-coupled Receptors

13.1K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
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Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

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G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
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Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

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Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
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G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

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GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
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Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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Related Experiment Video

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Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
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Nutritional and metabolic signalling through GPCRs.

Elisa Pardella1, Luigi Ippolito1, Elisa Giannoni1

  • 1Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Italy.

FEBS Letters
|July 1, 2022
PubMed
Summary

Metabolic molecules like lactate and fatty acids act as extracellular signals, activating G-protein-coupled receptors (GPCRs). Understanding these metabolite-sensing GPCRs is key for developing new treatments for diseases like diabetes and cancer.

Keywords:
G-protein-coupled receptorsextracellular signalling moleculeslactatemetabolitesnutrientssuccinate

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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
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Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay
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Area of Science:

  • Biochemistry
  • Cell Biology
  • Metabolic Diseases

Background:

  • Deregulated metabolism is central to diseases such as diabetes, obesity, and cancer.
  • Nutrients and metabolic intermediates function intracellularly for energy but are also released extracellularly.
  • Extracellular metabolites can act as hormone-like signaling molecules.

Purpose of the Study:

  • To review the role of specific metabolites (lactate, succinate, fatty acids, amino acids, ketogenesis/beta-oxidation intermediates) as extracellular signals.
  • To describe how metabolite-sensing G-protein-coupled receptors (GPCRs) integrate metabolic signals with cellular pathways.
  • To highlight GPCRs as potential therapeutic targets for metabolic diseases.

Main Methods:

  • Literature review of metabolic signaling.
  • Analysis of metabolite-sensing GPCR mechanisms.
  • Discussion of pathophysiological roles of extracellular metabolites.

Main Results:

  • Lactate, succinate, fatty acids, amino acids, and ketone bodies act as extracellular signaling molecules.
  • Metabolite-GPCR interactions modulate intracellular pathways.
  • These pathways are implicated in various diseases.

Conclusions:

  • Extracellular metabolites acting via GPCRs represent a critical signaling network.
  • Understanding these metabolite-GPCR axes is fundamental for disease research.
  • GPCRs offer novel druggable targets for treating metabolic disorders.