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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, Berkeley, United States.
Biorxiv : the Preprint Server for Biology
|September 16, 2024
Summary
Cells release microvesicles (MVs) after membrane damage. Calcium influx triggers annexin-containing MVs secretion, aiding plasma membrane repair and potentially serving as disease biomarkers.
Area of Science:
- Cell biology
- Biochemistry
- Membrane biology
Background:
- Microvesicles (MVs) are cell-derived particles involved in intercellular communication and disease biomarker discovery.
- The physiological triggers for microvesicle secretion remain largely unknown.
- Annexins are calcium-dependent phospholipid-binding proteins implicated in membrane repair.
Purpose of the Study:
- To investigate the mechanism of annexin-containing microvesicle secretion.
- To elucidate the role of calcium influx and calpains in microvesicle release.
- To propose a novel model for plasma membrane repair involving microvesicle secretion.
Main Methods:
- Isolation and characterization of annexin-containing microvesicles.
- Induction of plasma membrane damage and measurement of calcium influx.
- Analysis of annexin cleavage by calpains in response to membrane injury.
Main Results:
- Plasma membrane damage triggers calcium influx, leading to annexin recruitment and formation of a scab-like structure.
- Calpains cleave recruited annexins, disabling the scab and promoting annexin secretion within MVs.
- Annexin-containing MVs are released as a consequence of calcium-mediated plasma membrane repair.
Conclusions:
- A new model of plasma membrane repair is proposed, involving calpain-mediated cleavage of annexins and subsequent MV secretion.
- Elevated levels of these MVs are anticipated in cells with plasma membrane damage, such as muscle and metastatic cancer cells.
- This study reveals a novel pathway for microvesicle biogenesis linked to cellular injury and repair.
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