Intracellular membrane fusion is mediated by the SNARE (soluble N-ethylmale
imide-sensitive factor attachment protein receptor) proteins. All vesicle t
ransport steps also have an essential requirement for a member of the Sec1
protein family, including the neuronal Munc18-1 (also known as nSec1) in re
gulated exocytosis. Here, in adrenal chromaffin cells, we expressed a Munc1
8 mutant with reduced affinity for syntaxin, which specifically modified th
e kinetics of single-granule exocytotic release events, consistent with an
acceleration of fusion pore expansion, Thus, Munc18 functions in a late sta
ge in the fusion process, where its dissociation from syntaxin determines t
he kinetics of postfusion events.