Munc18-1 promotes large dense-core vesicle docking

被引:293
作者
Voets, T
Toonen, RF
Brian, EC
de Wit, H
Moser, T
Rettig, J
Südhof, TC
Neher, E
Verhage, M
机构
[1] Max Planck Inst Biophys Chem, Dept Membrane Biophys, D-37077 Gottingen, Germany
[2] Univ Gottingen, Sch Med, Dept Otolaryngol, D-37073 Gottingen, Germany
[3] Univ Utrecht, Med Ctr, Mol Neurosci Rudolf Magnus Inst, NL-3584 CG Utrecht, Netherlands
[4] Univ Texas, SW Med Ctr, Dept Mol Genet, Dallas, TX 75235 USA
[5] Univ Texas, SW Med Ctr, Ctr Basic Neurosci, Howard Hughes Med Inst, Dallas, TX 75235 USA
关键词
D O I
10.1016/S0896-6273(01)00391-9
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Secretory vesicles dock at the plasma membrane before Ca2+ 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.
引用
收藏
页码:581 / 591
页数:11
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