Annexin-Phospholipid Interactions in Membrane Fusion

Abstract

Cellular secretion is a membrane fusion event of utmost importance. The Ca2+ ion is critical in this process and its intracellular concentration is highly regulated. Therefore, Ca2+ may play a direct or indirect role in these intracellular membrane fusion processes. One early indication of a direct role in membrane fusion was the observation that Ca2+ could induce aggregation and leakage of contents from model membrane vesicles composed of the most abundant naturally occuring acidic phospholipid, phosphatidylserine (PS) (Papahadjopoulos and Bangham, 1966) and that these phenomena were associated with fusion of the vesicles (Papahadjopoulos et al., 1974). Subsequently, the ability to produce large unilamellar vesicles (LUV) (Szoka and Papahadjopoulos, 1978; Szoka et al., 1980; Wilschut et al., 1980) and the development of fluorescent fusion assays (Wilschut et al., 1980; Ellens et al., 1985) has allowed detailed studies of the factors that mediate Ca2+-dependent membrane fusion, particularly fusion of PS vesicles (Wilschut et al., 1980). A simple mass action model for the kinetics of membrane fusion, that could describe or predict the results of fusion assays under certain conditions, resulted from such studies (Nir et al., 1980a; Bentz et al., 1983).