Fig. 2. Model of membrane domain stabilization mediated by annexin A2. The model takes into account the Ca²⁺-dependent binding of annexin-A2–S100A10 to acidic phospholipids, which is mediated through the annexin core domain (left). Lateral diffusion could then direct the complex to raft membrane domains rich in cholesterol, glycosphingolipids and certain phosphatidylinositol phosphates, in particular phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P₂]. This could result in an annexin-A2–S100A10 fraction not requiring external Ca²⁺ for raft lipid binding. Following this raft recruitment, lateral annexin-annexin interactions, possibly regulated by Ca²⁺, could lead to the formation of a protein scaffold beneath the membrane and the concomitant clustering of rafts and recruitment of F-actin.