Related Experiment Video

Updated: May 2, 2026

Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels
16:36

Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels

Published on: May 19, 2009

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Sustained activation of P2X7 induces MMP-2-evoked cleavage and functional purinoceptor inhibition

Christopher N J Young1, Natalia Chira2, Justyna Róg3

  • 1School of Allied Health Sciences, Faculty of Health and Life Sciences, De Montfort University, Leicester, UK.

Journal of Molecular Cell Biology
|October 10, 2017
PubMed

Insights

Sustained P2X7 receptor activation releases matrix metalloproteinase 2 (MMP-2), which inhibits P2X7 channel and pore functions. This feedback loop impacts cell survival and offers therapeutic strategies for inflammatory diseases and cancers.

Area of Science:

  • Cell biology
  • Immunology
  • Pharmacology

Background:

  • The P2X7 purinoceptor's role in cell survival or death is stimulus-dependent, but mechanisms are unclear.
  • Extracellular adenosine triphosphate (ATP) intensity dictates P2X7 receptor function via its ion channel or large pore (LP).

Purpose of the Study:

  • To elucidate the mechanisms controlling P2X7 receptor functional divergence.
  • To investigate the role of matrix metalloproteinase 2 (MMP-2) in P2X7 receptor regulation.

Main Methods:

  • Investigated P2X7 receptor activation and function in various cell types (macrophages, myoblasts, HEK293, tumor cells).
  • Assessed the impact of sustained ATP stimulation on P2X7 receptor activity and MMP-2 release.
  • Examined MMP-2-dependent receptor cleavage and its effect on ion channel and LP functions.
  • Evaluated P2X7 receptor and MMP-2 activity in vivo using inflamed dystrophic muscle models.

Main Results:

  • Discovered a feedback loop where sustained P2X7 activation triggers MMP-2 release.
  • MMP-2 cleaves and inhibits P2X7 receptor ion channel and LP functions across diverse cell types.
  • This MMP-2 mediated inhibition protects cells from ATP-induced cytotoxicity, particularly in high P2X7-expressing cells.
  • P2X7 receptor ablation reduced gelatinase activity in inflamed dystrophic muscles in vivo.

Conclusions:

  • A novel MMP-2-mediated feedback mechanism fine-tunes P2X7 receptor activity.
  • This pathway involves both cell-autonomous and external factors, influencing P2X7 responses in vivo.
  • P2X7 antagonists represent a potential therapeutic strategy, offering an alternative to toxic MMP inhibitors for inflammatory diseases and cancers.

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