Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair.
Bottom Line: Compared with wild-type mouse perivascular cells, AnxA5- cells exhibit a severe membrane repair defect.In contrast, an AnxA5 mutant that lacks the ability of forming 2D arrays is unable to promote membrane repair.We propose that AnxA5 participates in a previously unrecognized step of the membrane repair process: triggered by the local influx of Ca(2+), AnxA5 proteins bind to torn membrane edges and form a 2D array, which prevents wound expansion and promotes membrane resealing.
Affiliation: Molecular Imaging and NanoBioTechnology, IECB, UMR-5248 CBMN CNRS-University Bordeaux1-ENITAB, Talence F-33402, France.Show MeSH
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Mentions: According to current models, membrane resealing is an active process that requires extracellular Ca2+, intracellular vesicles and a step of Ca2+-dependent exocytosis1349. We propose that immediately after membrane rupture (Fig. 7a,b), AnxA5 participates in a previously unrecognized step of the repair process (Fig. 7c,d), which is followed by the membrane fusion events (Fig. 7e). Membrane ruptures create microenvironments in which extracellular and intracellular components mix; in particular, the high intracellular concentrations of PS and AnxA5 mix with the high extracellular concentration of Ca2+. Triggered by the local increase in Ca2+ concentration, AnxA5 binds to PS molecules exposed at the edges of torn membranes at which it self-assembles into 2D arrays. In vitro studies have indicated that AnxA5 2D arrays rigidify lipid monolayers and reduce the lateral diffusion of phospholipids4546. We propose that the formation of AnxA5 2D array at a ruptured membrane strengthens the membrane and prevents the expansion of the tear. By counteracting membrane tension due to cytoskeleton attachment, AnxA5 2D arrays promote membrane resealing in a way similar to that of other agents that lower membrane tension, similar to cytoskeleton depolymerizers7 or surfactants78.
Affiliation: Molecular Imaging and NanoBioTechnology, IECB, UMR-5248 CBMN CNRS-University Bordeaux1-ENITAB, Talence F-33402, France.