Annexins and ATP in membrane traffic: a comparison with membrane fusion machinery

Annexins, calcium- and membrane-binding multifunctional proteins, have been implicated in N-ethylmaleimide (NEM)-independent fusion of vesicular structures involved in membrane traffic. This view is based on intracellular localization of annexins, which are frequently associated with endosomes, chromaffin granules, caveolae, clathrin-coated pits, and other membrane compartments, engaged in endo- and exocytosis. Moreover, annexins were found to modulate budding and aggregation of vesicle membranes, to interact with cytoskeletal proteins, and, upon binding to membranes, to change the structure of lipid bilayer, leading to membrane fusion. In addition, some annexins are substrates for various protein kinases and, in membrane-bound form, reveal calcium channel activity. Recently, annexins were observed to interact in vitro and in vivo with nucleotides, ATP, GTP or cAMP, which are potent mediators of membrane traffic processes. In addition, annexin VII showed hydrolytic activity towards GTP, and similarities in the mechanism of action to that of small GTP-binding proteins were found. The aim of the present review is to summarize the observations implying annexins as possible effectors in endo- and exocytosis and to compare them with well known complexes of cytosolic and membrane proteins forming the true membrane fusion machinery within a cell, conserved from yeast to the neurons of humans.