The synaptotagmin 1 linker may function as an electrostatic zipper that opens for docking but closes for fusion pore opening
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Syt1 (synaptotagmin 1), a major Ca2+ sensor for fast neurotransmitter release, contains tandem Ca2+-binding C2 domains (C2AB), a single transmembrane α-helix and a highly charged 60-residue-long linker in between. Using single-vesicle-docking and content-mixing assays we found that the linker region of Syt1 is essential for its two signature functions: Ca2+-independent vesicle docking and Ca2+-dependent fusion pore opening. The linker contains the basic-amino-acid-rich N-terminal region and the acidic-amino-acid-rich C-terminal region. When the charge segregation was disrupted, fusion pore opening was slowed, whereas docking was unchanged. Intramolecular disulfide cross-linking between N- and C-terminal regions of the linker or deletion of 40 residues from the linker reduced docking while enhancing pore opening, although the changes were subtle. EPR analysis showed Ca2+-induced line broadening reflecting a conformational change in the linker region. Thus the results of the present study suggest that the electrostatically bipartite linker region may extend for docking and fold to facilitate pore opening.
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Subsequent work revealed major differences between using the soluble C2AB fragment and reconstituted, full-length Syt1.
“Moreover, subsequent work revealed major differences between using the soluble C2AB fragment and reconstituted, full-length Syt184,85.”
From Architecture of the synaptotagmin–SNARE machinery for neuronal exocytosis (2015) · cites this paper as [84]
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- Authors
- Lai, Y., Lou, X., Jho, Y., Yoon, T.-Y., & Shin, Y.-K.
- Affiliations
- Iowa State University (US)
- Pohang University of Science and Technology (KR)
- Korea Advanced Institute of Science and Technology (KR)
- Corresponding author
- Lai, Ying
- Lou, Xiaochu
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2013-10-24
- Volume
- 456
- Issue
- 1
- Pages
- 25-33
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC4418238
- OpenAlex
- W2324695254
- Semantic Scholar
- 2aebb239038719ba8985c4b7ebf686f74c3b20eb
- Cited by
- 28
- References
- 36
- Citations by year
- 2026: 2 · 2025: 2 · 2022: 1 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 8 · 2014: 4
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical Journal (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Illinois at Urbana-Champaign
- National Institute of General Medical Sciences (R01GM051290)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Keywords
- synaptotagmin-1, vesicle docking, neurotransmitter release, C2 domain, charge segregation, disulfide cross-linking, content mixing
- MeSH terms
- Animals, Calcium, Cations, Divalent, Cross-Linking Reagents, Disulfides, Lipids, Membrane Fusion, Membranes, Artificial, Protein Conformation, Synaptic Vesicles, Mutagenesis, Site-Directed, SNARE Proteins, Synaptotagmin I, Rats, Static Electricity
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