Abstract
The absence of a cell wall affords animal cells diverse functionality at the cost of acute sensitization to plasma membrane (PM) damage. Thus, animal cells tightly monitor and maintain the integrity of their PM to prevent cell death. Genetic loss of PM repair factors is associated with human diseases including muscular dystrophy and neurodegeneration. Despite evidence that annexin and endosomal sorting complex required for transport (ESCRT) proteins are required for PM repair, the extent to which their recruitment is coordinated at sites of membrane damage is unclear. Here, we identify sorcin as a new PM repair factor that directly couples annexin A11 (ANXA11)-mediated sensing of PM damage and ESCRT-III assembly. We demonstrate that ANXA11, recruited to the PM upon damage-induced calcium influx, serves as an anchor that facilitates the sequential recruitment of sorcin and ESCRT-III at PM lesions. Our data highlight mechanistic and topological similarities between the budding of membrane-enveloped viruses and damage-induced microvesicles. We propose that they share a common mechanism of membrane budding and speculate that membrane-enveloped viruses may have co-opted this host pathway of PM ESCRT recruitment to facilitate virion assembly and propagation.