Evaluation of the annexins as potential mediators of membrane fusion in exocytosis

Abstract

Membrane fusion is a central event in the process of exocytosis. It occurs between secretory vesicle membranes and the plasma membrane and also among secretory vesicle membranes themselves during compound exocytosis. In many cells the fusion event is regulated by calcium. Since the relevant membranes do not undergo fusion in vitro when highly purified, much attention has been paid to possible protein mediators of these calcium-dependent fusion events. The annexins comprise a group of calcium-dependent membrane-aggregating proteins, of which synexin is the prototype, which can initiate contacts between secretory vesicle membranes which will then fuse if the membranes are further perturbed by the addition of exogenous free fatty acids. This review discusses the secretory pathway and the evidence obtained from in vitro studies that suggests the annexins may be mediators or regulators of membrane fusion in exocytosis.

Properties and Partial Protein Sequence of Plant Annexins

“…It is, therefore, of interest that none of the sequences for annexins from either maize (this work) or tomato (25) (4) or secretory vesicles at levels of free Ca2+ that are outside the accepted physiological range for plant cells (18,29). There is, however, some doubt as to whether averaged values for cytosolic free Ca2" adequately reflect the changes in free Ca2" that are likely to occur in the immediate vicinity of the fusion site at the plasma membrane (30). Also, we have previously noted that the binding of annexins to artificial liposomes is dependent on both the free Ca2" concentration and pH (4).…”

“…Another line of evidence is that, in tip-growing pollen tubes, Ca2+ can influence both the rate of pollen tube growth and the propensity for vesicles to fuse with the plasma membrane (21,26). In animal cells, a number of proteins have been implicated in the regulation of exocytosis, including members of a novel family of Ca2"-binding proteins known as annexins (10,30).…”

“…Although annexins are not directly fusogenic, the concept that they may mediate exocytotic events is based in part on evidence that, in the presence of Ca2", annexin II can bind to, aggregate, and (in conjunction with arachidonic acid and low pH) fuse secretory vesicle membranes (2,30).…”

“…The sequence data for the third annexin-like protein p23 has no apparent homology with annexins, although the protein shows very sensitive Ca2"-dependent binding to phospholipids. To investigate the biological role of plant annexins, we determined whether p33 and p35 have, in common with annexins II and VI (30), the capacity to associate with cytoskeletal proteins. Our findings indicate that maize annexins preferentially bind to membrane lipid fractions in the presence of Ca2' and that there is no association between these annexins and either plant or animal F-actin.…”

Organisation of the chicken annexin V gene and its correlation with the tertiary structure of the protein

“…Annexins are a family of at least 12 membrane-associated proteins with high aflinity to calcium and phospholipids with diverse and partially known functions (for review see [1,2,3]). Although soluble in water, annexins associate intimately with cell membranes owing to their affinity for phospholipids in the presence of Ca2+ and are therefore classified a third class of amphiphatic membrane proteins [3].…”