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      Munc18-1 promotes large dense-core vesicle docking.

      Neuron
      Animals, Antigens, Surface, metabolism, Cattle, Cell Membrane, Chromaffin Cells, ultrastructure, Exocytosis, physiology, Female, Fetus, cytology, Gene Deletion, Gene Expression, Membrane Potentials, Mice, Mice, Mutant Strains, Microscopy, Electron, Munc18 Proteins, Nerve Tissue Proteins, genetics, Patch-Clamp Techniques, Pregnancy, Synaptic Vesicles, Syntaxin 1, Vesicular Transport Proteins

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          Abstract

          Secretory vesicles dock at the plasma membrane before Ca(2+) triggers their exocytosis. Exocytosis requires the assembly of SNARE complexes formed by the vesicle protein Synaptobrevin and the membrane proteins Syntaxin-1 and SNAP-25. We analyzed the role of Munc18-1, a cytosolic binding partner of Syntaxin-1, in large dense-core vesicle (LDCV) secretion. Calcium-dependent LDCV exocytosis was reduced 10-fold in mouse chromaffin cells lacking Munc18-1, but the kinetic properties of the remaining release, including single fusion events, were not different from controls. Concomitantly, mutant cells displayed a 10-fold reduction in morphologically docked LDCVs. Moreover, acute overexpression of Munc18-1 in bovine chromaffin cells increased the amount of releasable vesicles and accelerated vesicle supply. We conclude that Munc18-1 functions upstream of SNARE complex formation and promotes LDCV docking.

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