Synaptotagmin-1 Is an Antagonist for Munc18-1 in SNARE Zippering |
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Authors: | Xiaochu Lou Jaeil Shin Yoosoo Yang Jaewook Kim Yeon-Kyun Shin |
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Institution: | 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 |
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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 Ca2+ 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 Ca2+-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. |
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Keywords: | Exocytosis Fusion Protein Membrane Fusion Neurotransmitter Release Single Molecule Biophysics Soluble NSF Attachment Protein Receptor (SNARE) |
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