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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...
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Related Experiment Video

Updated: May 24, 2026

Malachite Green Assay for the Discovery of Heat-Shock Protein 90 Inhibitors
07:57

Malachite Green Assay for the Discovery of Heat-Shock Protein 90 Inhibitors

Published on: January 20, 2023

Hsp90 depletion goes wild.

Mark L Siegal1, Joanna Masel

  • 1Center for Genomics and Systems Biology, Department of Biology, New York University, 12 Waverly Place, New York, NY 10003, USA. mark.siegal@nyu.edu

BMC Biology
|February 29, 2012
PubMed
Summary

A newly discovered Drosophila allele downregulates Heat Shock Protein 90 (Hsp90), revealing cryptic genetic variation in the wild. This finding highlights the importance of Hsp90 levels for evolutionary adaptation.

Area of Science:

  • Evolutionary Biology
  • Genetics
  • Molecular Biology

Background:

  • Heat Shock Protein 90 (Hsp90) is known to buffer genetic variation in laboratory settings.
  • The ecological relevance of Hsp90's role in phenotypic variation has remained largely unexplored in natural populations.

Purpose of the Study:

  • To investigate whether Hsp90 downregulation plays a role in revealing cryptic genetic variation in wild Drosophila populations.
  • To determine the evolutionary significance of naturally occurring Hsp90 alleles.

Main Methods:

  • Identification and characterization of a naturally occurring Drosophila allele associated with reduced Hsp90 levels.
  • Assessing the phenotypic consequences of this allele, specifically its impact on the manifestation of cryptic genetic variation.

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  • Comparing the effects of naturally occurring Hsp90 downregulation with experimentally induced extreme depletion.

    • Main Results:

    • A naturally occurring Drosophila allele was found to downregulate Hsp90, leading to increased sensitivity to cryptic genetic variation.
    • The magnitude of Hsp90 downregulation appears critical, as extreme depletion may cause additional effects like transposable element reactivation or aneuploidy.
    • This suggests a mechanism by which environmental pressures could uncover hidden genetic diversity.

    Conclusions:

    • Naturally occurring Hsp90 alleles can influence evolutionary trajectories by modulating the expression of cryptic genetic variation.
    • Hsp90's role extends beyond laboratory buffering, impacting adaptation in wild populations.
    • Understanding the precise levels of Hsp90 is crucial for predicting its evolutionary consequences.