Abstract
Sec1/Munc18 (SM) proteins are required for every step of intracellular membrane fusion, but their molecular mechanism of action has been unclear. In this work, we demonstrate a fundamental role of the SM protein: to act as a stimulatory subunit of its cognate SNARE fusion machinery. In a reconstituted system, mammalian SNARE pairs assemble between bilayers to drive a basal fusion reaction. Munc18-1/nSec1, a synaptic SM protein required for neurotransmitter release, strongly accelerates this reaction through direct contact with both t- and v-SNAREs. Munc18-1 accelerates fusion only for the cognate SNAREs for exocytosis, therefore enhancing fusion specificity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Exocytosis
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Humans
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Membrane Fusion
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Mice
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Models, Biological
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Molecular Sequence Data
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Multiprotein Complexes / metabolism
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Munc18 Proteins / metabolism*
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Mutation / genetics
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Neurons / cytology
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Protein Binding
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Protein Subunits / metabolism
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Rats
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SNARE Proteins / metabolism*
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Syntaxin 1 / chemistry
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Syntaxin 1 / metabolism
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Vesicle-Associated Membrane Protein 2 / chemistry
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Vesicle-Associated Membrane Protein 2 / genetics
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Vesicle-Associated Membrane Protein 2 / metabolism
Substances
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Multiprotein Complexes
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Munc18 Proteins
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Protein Subunits
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SNARE Proteins
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Syntaxin 1
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Vesicle-Associated Membrane Protein 2