Figure 5.

Model for annexin 2-mediated myoblast cell membrane repair. Summary of events (1–4) involved in myoblast membrane repair based on results of this study. (1) In the uninjured cell, AnxA2 is distributed diffusely in the cytosol, while cholesterol microdomains and associated dysferlin are distributed diffusely in the plasma membrane. Additionally, dysferlin also localizes on intracellular vesicles. (2) Injury to the cell membrane induces rapid influx of extracellular Ca²⁺ ions through the ruptured membrane followed by cholesterol accumulation at the injury site, AnxA2 phosphorylation, leading to its association with dysferlin and plasma membrane lipids and cholesterol-rich microdomains. (3) AnxA2 binding promotes fusion of dysferlin-containing vesicles with the injured membrane. (4) Through the cholesterol and AnxA2-mediated exocytosis of dysferlin-containing vesicles, the cell membrane level of dysferlin increases concomitantly with the repair of the wounded membrane. This allows the cell to return to a pre-injury state with redistribution of AnxA2, cholesterol, and dysferlin to their resting state. Impairment in any step of this repair pathway—reduction in AnxA2, lack of calcium influx, cholesterol depletion, or impairment of Annexin 2 phosphorylation—interferes with myoblast membrane repair.