Damage control: cellular mechanisms of plasma membrane repair

When wounded, eukaryotic cells reseal in a few seconds. Ca2+ influx induces exocytosis of lysosomes, a process previously thought to promote repair by 'patching' wounds. New evidence suggests that resealing involves direct wound removal. Exocytosis of lysosomal acid sphingomyelinase (ASM) triggers endocytosis of lesions followed by intracellular degradation. Characterization of injury-induced endosomes revealed a role for caveolae, sphingolipid-enriched plasma membrane invaginations that internalize toxin pores and are abundant in mechanically stressed cells. These findings provide a novel mechanistic explanation for the muscle pathology associated with mutations in caveolar proteins. Membrane remodeling by the ESCRT complex was also recently shown to participate in small-wound repair, emphasizing that cell resealing involves previously unrecognized mechanisms for lesion removal that are distinct from the patch model.