Regulated vesicular fusion in neurons: snapping together the details

In the past year major strides have been made toward our understanding of the molecular mechanisms involved in regulated vesicle fusion and exocytosis in neurons and neuroendocrine cells. Much of this advance has come from the identification of proteins participating in these events and of their potential roles mediated by interactions with each other, the constituent membranes, and, in some cases, Ca2+ signaling. The involvement of vesicle fusion in elongation of neuronal processes during development and release of transmitters and neuromodulatory peptides in the mature nervous system indicates, however, that refinements in the fusion machinery may be required for each of these acts. For many of the participants in synaptic membrane fusion, variant isoforms have been identified that exhibit modifications that might alter interactive properties of these proteins. We discuss the idea that diversification of isoforms, as illustrated by the expression of alternatively spliced variants of SNAP-25, is likely to be an important component in providing the detail necessary to differentiate the physiology of regulated fusion of different classes of vesicles employed in development, neurotransmission, and secretion.