Control of fusion pore dynamics during exocytosis by Munc18.
Intracellular membrane fusion is mediated by the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins. All vesicle transport steps also have an essential requirement for a member of the Sec1 protein family, including the neuronal Munc18-1 (also known as nSec1) in regulated exocytosis. Here, in adrenal chromaffin cells, we expressed a Munc18 mutant with reduced affinity for syntaxin, which specifically modified the kinetics of single-granule exocytotic release events, consistent with an acceleration of fusion pore expansion. Thus, Munc18 functions in a late stage in the fusion process, where its dissociation from syntaxin determines the kinetics of postfusion events.
Fisher
R J
RJ
Physiological Laboratory, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK.
Pevsner
J
J
Burgoyne
R D
RD
D000200:Action Potentials; D000313:Adrenal Medulla / Q000166:cytology; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000502:physiology*; D005089:Exocytosis; D008561:Membrane Fusion; D051938:Munc18 Proteins; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D022142:Secretory Vesicles / Q000502:physiology*; D050827:Syntaxin 1; D014162:Transfection; D033921:Vesicular Transport Proteins
D000954:Antigens, Surface; D002395:Catecholamines; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; C497939:Stxbp1 protein, rat; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins