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Cell. 2009 Sep 4;138(5):935-46. doi: 10.1016/j.cell.2009.07.027. Epub 2009 Aug 27.

Synaptotagmin-1 docks secretory vesicles to syntaxin-1/SNAP-25 acceptor complexes.

Author information

1
Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam and VU Medical Center, 1081 HV Amsterdam, the Netherlands.

Abstract

Docking, the initial association of secretory vesicles with the plasma membrane, precedes formation of the SNARE complex, which drives membrane fusion. For many years, the molecular identity of the docked state, and especially the vesicular docking protein, has been unknown, as has the link to SNARE complex assembly. Here, using adrenal chromaffin cells, we identify the vesicular docking partner as synaptotagmin-1, the calcium sensor for exocytosis, and SNAP-25 as an essential plasma membrane docking factor, which, together with the previously known docking factors Munc18-1 and syntaxin, form the minimal docking machinery. Moreover, we show that the requirement for Munc18-1 in docking, but not fusion, can be overcome by stabilizing syntaxin/SNAP-25 acceptor complexes. These findings, together with cross-rescue, double-knockout, and electrophysiological data, lead us to propose that vesicles dock when synaptotagmin-1 binds to syntaxin/SNAP-25 acceptor complexes, whereas Munc18-1 is required for the downstream association of synaptobrevin to form fusogenic SNARE complexes.

PMID:
19716167
DOI:
10.1016/j.cell.2009.07.027
[Indexed for MEDLINE]
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