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Related Concept Videos

GPCR Desensitization01:12

GPCR Desensitization

6.1K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
6.1K
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

5.5K
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...
5.5K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

6.9K
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...
6.9K
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

12.5K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
12.5K
Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

9.0K
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,...
9.0K
Carrier-Mediated Transport01:06

Carrier-Mediated Transport

1.6K
Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
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Related Experiment Video

Updated: May 5, 2026

Cholesterol Efflux Assay
07:54

Cholesterol Efflux Assay

Published on: March 6, 2012

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A Druggable G Protein Checkpoint in Cholesterol Efflux.

Gajanan D Katkar, Mahitha Shree Anandachar, Celia R Espinoza

    Biorxiv : the Preprint Server for Biology
    |February 27, 2026
    PubMed
    Summary

    Lipid-associated macrophages drive immunometabolic diseases by failing to clear lipids. Targeting a GIV-dependent brake restores cholesterol efflux, reversing plaque buildup and establishing reverse cholesterol transport as a new therapy.

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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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    A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

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    Enrichment of Mammalian Tissues and Xenopus Oocytes with Cholesterol
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    Enrichment of Mammalian Tissues and Xenopus Oocytes with Cholesterol

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    Related Experiment Videos

    Last Updated: May 5, 2026

    Cholesterol Efflux Assay
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    Cholesterol Efflux Assay

    Published on: March 6, 2012

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    A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
    07:41

    A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

    Published on: February 20, 2018

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    Enrichment of Mammalian Tissues and Xenopus Oocytes with Cholesterol
    10:12

    Enrichment of Mammalian Tissues and Xenopus Oocytes with Cholesterol

    Published on: March 25, 2020

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    Area of Science:

    • Immunometabolism and Atherosclerosis Research
    • Macrophage Biology and Lipid Metabolism

    Background:

    • Immunometabolic diseases like obesity and atherosclerosis stem from lipid-associated macrophages (LAMs) accumulating excess lipids.
    • Reverse cholesterol transport (RCT), the primary pathway for lipid clearance by macrophages, is currently not a viable therapeutic target.

    Purpose of the Study:

    • To identify molecular mechanisms underlying LAM dysfunction in driving plaque progression.
    • To explore GIV (CCDC88A) as a potential therapeutic target for restoring RCT and treating immunometabolic diseases.

    Main Methods:

    • Integrated systems modeling with human plaque transcriptomes to identify key LAM subpopulations.
    • Utilized myeloid-specific GIV deletion in murine models to assess its impact on plaque burden and lipid mobilization.
    • Investigated the mechanistic role of GIV in trapping ABCA1 and modulating Gαi-cAMP signaling.

    Main Results:

    • GIV was identified as a molecular brake on RCT, with its deletion reducing aortic plaque burden and mobilizing lipids.
    • GIV was shown to trap the ABCA1 transporter and suppress cAMP/PKA-CREB signaling, inhibiting cholesterol efflux.
    • Disrupting the GIV●Gαi checkpoint restored ABCA1 activity, reprogrammed LAMs, and significantly reduced modeled plaque-progression risk.

    Conclusions:

    • Restoring RCT by targeting the GIV●Gαi-cAMP checkpoint offers a novel, macrophage-intrinsic therapeutic strategy for immunometabolic diseases.
    • This approach successfully restored cholesterol efflux where conventional therapies like statins and beta-blockers failed.
    • The findings establish RCT restoration as a druggable paradigm for treating conditions driven by dysfunctional lipid metabolism in macrophages.