title: Synaptotagmin-1 is an antagonist for Munc18-1 in SNARE zippering.
abstract: In neuroexocytosis, SNAREs and Munc18-1 may consist of the minimal membrane fusion machinery. Consistent with this notion, we observed, using single molecule fluorescence assays, that Munc18-1 stimulates SNARE zippering and SNARE-dependent lipid mixing in the absence of a major Ca(2+) sensor synaptotagmin-1 (Syt1), providing the structural basis for the conserved function of Sec1/Munc18 proteins in exocytosis. However, when full-length Syt1 is present, no enhancement of SNARE zippering and no acceleration of Ca(2+)-triggered content mixing by Munc18-1 are observed. Thus, our results show that Syt1 acts as an antagonist for Munc18-1 in SNARE zippering and fusion pore opening. Although the Sec1/Munc18 family may serve as part of the fusion machinery in other exocytotic pathways, Munc18-1 may have evolved to play a different role, such as regulating syntaxin-1a in neuroexocytosis.
authors.affiliation: From the Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa 50011 and.
authors.forename: Xiaochu
authors.initials: X
authors.lastname: Lou
authors.affiliation: From the Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa 50011 and.
authors.forename: Jaeil
authors.initials: J
authors.lastname: Shin
authors.affiliation: the Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 6, Seongbuk-gu, Seoul 136-791, South Korea.
authors.forename: Yoosoo
authors.initials: Y
authors.lastname: Yang
authors.affiliation: the Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 6, Seongbuk-gu, Seoul 136-791, South Korea.
authors.forename: Jaewook
authors.initials: J
authors.lastname: Kim
authors.affiliation: From the Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa 50011 and the Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 6, Seongbuk-gu, Seoul 136-791, South Korea colishin@iastate.edu.
authors.forename: Yeon-Kyun
authors.initials: YK
authors.lastname: Shin
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007700:Kinetics; D008561:Membrane Fusion; D051938:Munc18 Proteins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D011510:Proteolipids / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000737:chemistry / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics / Q000378:metabolism; D050863:Synaptotagmin I / Q000235:genetics* / Q000378:metabolism; D050827:Syntaxin 1 / Q000235:genetics / Q000378:metabolism; D050988:Vesicle-Associated Membrane Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D051938:Munc18 Proteins; D011510:Proteolipids; D011994:Recombinant Proteins; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D050863:Synaptotagmin I; D050827:Syntaxin 1; C494312:Syt1 protein, rat; C494706:Vamp2 protein, rat; D050988:Vesicle-Associated Membrane Protein 2; C020485:proteoliposomes; D002118:Calcium
keywords: Exocytosis; Fusion Protein; Membrane Fusion; Neurotransmitter Release; Single Molecule Biophysics; Soluble NSF Attachment Protein Receptor (SNARE)