Modulation of annexin VI-driven aggregation of phosphatidylserine liposomes by ATP

Abstract

Annexin (Anx) VI has been implicated in mediating the endosome aggregation and vesicle fusion in secreting epithelia during exocytosis. In addition, Anx VI of porcine liver is an ATP-binding protein, and ATP in vitro modulates its interaction with membranes and cytoskeletal elements (Bandorowicz-Pikula and Awasthi, FEBS Lett. 409 (1997) 300–306). In this study, we examined the effect of ATP on phosphatidylserine (PtdSer) aggregation in the presence of annexin and on calcium-dependent binding of protein to liposomes, and found that ATP stimulates the former process, although it increases the calcium concentration necessary for half-maximal binding of Anx VI to membranes. These results were corroborated by the experiments with fluorescent analog of ATP, in which binding of ATP to Anx VI was affected by binding of Ca 2+ and/or phospholipids to the protein. Taken together they favour an idea of ATP being a functional ligand for Anx VI, which even in the relative absence of Ca 2+ may modulate interaction of Anx VI with PtdSer-enriched membranes.