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Updated: Aug 10, 2026

Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
09:40

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Published on: September 20, 2011

Chemokine receptor CCR5 functionally couples to inhibitory G proteins and undergoes desensitization

J Zhao1, L Ma, Y L Wu

  • 1Shanghai Institute of Cell Biology, Chinese Academy of Sciences, People's Republic of China.

Journal of Cellular Biochemistry
|September 15, 1998
PubMed

Insights

Chemokine receptor 5 (CCR5) couples to inhibitory G proteins, mediating leukocyte chemotaxis and HIV-1 entry. This study shows CCR5 activation leads to G-protein signaling, desensitization, and internalization.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Immunology

Background:

  • Chemokine receptor CCR5 is crucial for leukocyte migration.
  • CCR5 also serves as a key coreceptor for HIV-1 infection.
  • Understanding CCR5 signaling is vital for therapeutic development.

Purpose of the Study:

  • To investigate CCR5-mediated signaling events.
  • To determine the G-protein coupling of CCR5.
  • To characterize CCR5 desensitization and internalization.

Main Methods:

  • Stable and transient expression of hemagglutinin epitope-tagged human CCR5.
  • Flow cytometry for surface receptor expression analysis.
  • Assays for G-protein activation ([35S]GTPgammaS binding) and adenylyl cyclase activity.
  • Pertussis toxin treatment and Gialpha2 overexpression studies.

Main Results:

  • CCR5 agonist RANTES stimulated G-protein activation and inhibited adenylyl cyclase activity in a CCR5-dependent manner.
  • RANTES-induced signaling was blocked by pertussis toxin, indicating involvement of inhibitory G proteins.
  • Overexpression of Gialpha2 enhanced RANTES-dependent signaling.
  • CCR5 signaling exhibited rapid desensitization and agonist-dependent receptor internalization upon prolonged RANTES exposure.

Conclusions:

  • CCR5 functionally couples to membrane-associated inhibitory G proteins, specifically Gialpha2.
  • CCR5 signaling is subject to rapid agonist-dependent desensitization and internalization.
  • These findings provide insights into CCR5 regulation and its role in HIV-1 infection.

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