Role of Munc18-1 in synaptic vesicle and large dense-core vesicle secretion.

SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex formation between a vesicle and the target membrane is a central aspect of probably all vesicle fusion reactions. The sec1/munc18 (SM) protein family is also involved in membrane trafficking and fusion events. However, in contrast with the consensus on SNARE protein function, analysis of SM proteins in different systems has produced different ideas about their exact role, their site of action and their relationship to SNARE proteins. Deletion of the SM protein involved in secretory vesicle release in mice, Munc18-1, results in a complete block of exocytosis. Manipulation of Munc18-1 protein levels in neurons and adrenal chromaffin cells argues for a positive role of this protein in vesicle secretion, as overexpression results in an increase in vesicle secretion. A decrease in Munc18-1 protein levels, on the other hand, leads to a decrease in vesicle secretion.