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Related Concept Videos

Spare Receptors01:30

Spare Receptors

Some receptors remain unoccupied even when an agonist produces a maximal response. Such empty ones are called spare receptors. In presence of spare receptors the maximum effect of an agonist drug is achieved with fewer than 100% of the receptors being occupied. To determine the presence of spare receptors, scientists often compare the concentration of the drug needed to produce 50% of the maximum effect (EC50) with the concentration of the drug needed to occupy 50% of the receptors (Kd). If the...
Desensitization and Tachyphylaxis01:20

Desensitization and Tachyphylaxis

Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.
Several...
GPCR Desensitization01:12

GPCR Desensitization

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...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists01:23

Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists

Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.
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The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...

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Related Experiment Video

Updated: Jul 2, 2026

A High-content Assay for Monitoring AMPA Receptor Trafficking
10:34

A High-content Assay for Monitoring AMPA Receptor Trafficking

Published on: January 28, 2019

TARP redundancy is critical for maintaining AMPA receptor function.

Karen Menuz1, Jessica L O'Brien, Siavash Karmizadegan

  • 1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California 94143, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|August 30, 2008
PubMed
Summary

Transmembrane AMPA receptor regulatory proteins (TARPs) gamma-2 and gamma-3 are crucial for cerebellar function and AMPA receptor targeting. These TARPs also unexpectedly specify AMPA receptor subunit composition, highlighting their essential role in neuronal health.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Transmembrane AMPA receptor regulatory proteins (TARPs) are auxiliary subunits of AMPA receptors, modulating their function.
  • The complete physiological roles of TARPs in vivo are not fully understood.

Purpose of the Study:

  • To investigate the in vivo physiological roles of TARPs, specifically gamma-2 and gamma-3, in neuronal function.
  • To elucidate the impact of TARP deficiency on AMPA receptor localization, kinetics, and composition.

Main Methods:

  • Generation and analysis of double knock-out mice lacking TARPs gamma-2 and gamma-3.
  • Electrophysiological recordings and biochemical analyses of AMPA receptors in cerebellar Golgi cells.
  • Investigation of AMPA receptor subunit composition in knock-out models.

Main Results:

  • Mice lacking both TARPs gamma-2 and gamma-3 exhibit severe ataxia and failure to thrive.
  • TARPs gamma-2 and gamma-3 are critical for synaptic targeting and kinetics of AMPA receptors in cerebellar Golgi cells, with either subunit being sufficient for full function.
  • TARPs gamma-2 and gamma-3 unexpectedly determine the subunit composition of synaptic AMPA receptors.

Conclusions:

  • TARPs are essential for proper AMPA receptor localization and function in the central nervous system.
  • This study reveals a novel role for TARPs in regulating AMPA receptor assembly and subunit composition.
  • TARP deficiency leads to significant neurological deficits due to impaired AMPA receptor function.