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Calpains orchestrate secretion of annexin-containing microvesicles during membrane repair

Justin Krish Williams1, Jordan Matthew Ngo1, Abinayaa Murugupandiyan1

  • 1Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.

The Journal of Cell Biology
|May 16, 2025
PubMed

Insights

Cells release microvesicles (MVs) after plasma membrane damage. Calcium influx triggers annexin-containing MVs, aiding in cell repair and potentially indicating disease.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Membrane Biology

Background:

  • Microvesicles (MVs) are cell-derived particles with roles in intercellular communication and as disease biomarkers.
  • The physiological triggers for microvesicle secretion remain largely unknown.
  • Annexins are proteins involved in membrane repair.

Purpose of the Study:

  • To investigate the physiological processes that induce the secretion of annexin-containing microvesicles.
  • To elucidate the role of calcium influx and calpains in microvesicle formation and release.

Main Methods:

  • Isolation and characterization of annexin-containing microvesicles.
  • Induction of plasma membrane damage and observation of cellular response.
  • Analysis of annexin cleavage by calpains in response to calcium influx.

Main Results:

  • Plasma membrane damage and subsequent calcium influx trigger the secretion of annexin-containing microvesicles.
  • Calcium-bound annexins form a scab-like structure at the injury site.
  • Calpains cleave annexins, disabling scabbing and promoting their secretion within MVs.

Conclusions:

  • A novel model of plasma membrane repair involving calpain-mediated secretion of annexin-containing MVs is proposed.
  • Elevated secretion of these MVs is anticipated in cells with plasma membrane damage, such as muscle and metastatic cancer cells.
  • This mechanism highlights a new pathway for cellular repair and potential biomarker discovery.

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