Selective activation of cognate SNAREpins by Sec1/Munc18 proteins.
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.
Shen
Jingshi
J
Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA.
Tareste
David C
DC
Paumet
Fabienne
F
Rothman
James E
JE
Melia
Thomas J
TJ
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D005089:Exocytosis; D006801:Humans; D008561:Membrane Fusion; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D051938:Munc18 Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D050600:SNARE Proteins / Q000378:metabolism*; D050827:Syntaxin 1 / Q000737:chemistry / Q000378:metabolism; D050988:Vesicle-Associated Membrane Protein 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D046912:Multiprotein Complexes; D051938:Munc18 Proteins; D021122:Protein Subunits; D050600:SNARE Proteins; D050827:Syntaxin 1; D050988:Vesicle-Associated Membrane Protein 2