RT Journal Article
A1 Williams, Justin Krish
A1 Ngo, Jordan Matthew
A1 Murugupandiyan, Abinayaa
A1 Croall, Dorothy E.
A1 Hartzell, H. Criss
A1 Schekman, Randy
T1 Calpains orchestrate secretion of annexin-containing microvesicles during membrane repair
JF Journal of Cell Biology
JO J Cell Biol
YR 2025
DO 10.1083/jcb.202408159
OP e202408159
VO 224
IS 7
SN 0021-9525
AB Microvesicles (MVs) are membrane-enclosed, plasma membrane–derived particles released by cells from all branches of life. MVs have utility as disease biomarkers and may participate in intercellular communication; however, physiological processes that induce their secretion are not known. Here, we isolate and characterize annexin-containing MVs and show that these vesicles are secreted in response to the calcium influx caused by membrane damage. The annexins in these vesicles are cleaved by calpains. After plasma membrane injury, cytoplasmic calcium-bound annexins are rapidly recruited to the plasma membrane and form a scab-like structure at the lesion. In a second phase, recruited annexins are cleaved by calpains-1/2, disabling membrane scabbing. Cleavage promotes annexin secretion within MVs. Our data support a new model of plasma membrane repair, where calpains relax annexin-membrane aggregates in the lesion repair scab, allowing secretion of damaged membrane and annexins as MVs. We anticipate that cells experiencing plasma membrane damage, including muscle and metastatic cancer cells, secrete these MVs at elevated levels.
RD 5/24/2025
UL https://doi.org/10.1083/jcb.202408159