Ca2+-dependent and -independent activities of neural and non-neural synaptotagmins
Abstract
Synaptotagmins (Syts) are brain-specific Ca2+/phospholipid-binding proteins. In hippocampal synapses, Syt I is essential for fast Ca(2+)-dependent synaptic vesicle exocytosis but not for Ca(2+)-independent exocytosis. In vertebrates and invertebrates, Syt may therefore participate in Ca(2+)-dependent synaptic membrane fusion, either by serving as the Ca2+ sensor in the last step of fast Ca(2+)-triggered neurotransmitter release, or by collaborating with an additional Ca2+ sensor. While Syt I binds Ca2+ (refs 10, 11), its phospholipid binding is triggered at lower calcium concentrations (EC50 = 3-6 microM) than those required for exocytosis. Furthermore, Syts bind clathrin-AP2 with high affinity, indicating that they may play a general role in endocytosis rather than being confined to a specialized function in regulated exocytosis. Here we resolve this apparent contradiction by describing four Syts, three of which (Syt VI, VII and VIII) are widely expressed in non-neural tissues. All Syts tested share a common domain structure, with a cytoplasmic region composed of two C2 domains that interacts with clathrin-AP2 (Kd = 0.1-1.0 nM) and with neural and non-neural syntaxins. The first C2 domains of Syt I, II, III, V and VII, but not of IV, VI or VIII, bind phospholipids with a similar Ca(2+)-concentration dependence (EC50 = 3-6 microM). The same C2 domains also bind syntaxin as a function of Ca2+ but the Ca(2+)-concentration dependence of Syt I, II and V (> 200 microM) differs fro…
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Syt1 interacts with the neuronal SNARE complex.
“Syt1 also interacts with the neuronal SNARE complex based on immunoprecipitation and pull-downs24–27, single molecule fluorescence resonance energy transfer (smFRET)28, and nuclear magnetic resonance29,30 experiments.”
From Architecture of the synaptotagmin–SNARE machinery for neuronal exocytosis (2015) · cites this paper as [25]
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- Authors
- Li, C., Ullrich, B., Zhang, J. Z., Anderson, R. G. W., Brose, N., & Südhof, T. C.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- Venue
- Nature
- Published
- 1995-06
- Volume
- 375
- Issue
- 6532
- Pages
- 594-599
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2018757497
- Cited by
- 599
- References
- 2
- Citations by year
- 2026: 3 · 2025: 4 · 2023: 3 · 2022: 6 · 2021: 8 · 2020: 6 · 2019: 6 · 2018: 8 · 2017: 12 · 2016: 5 · 2015: 11 · 2014: 13 · 2013: 10 · 2012: 13
- FWCI
- 19.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- GRO (submittedVersion)
- 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 › Extracellular vesicles in disease
- Keywords
- synaptotagmin, calcium binding, phospholipid binding, C2 domain, syntaxin, synaptic vesicle exocytosis, neurotransmitter release, endocytosis, hippocampal synapses
- MeSH terms
- Amino Acid Sequence, Animals, Brain, Calcium, Calcium-Binding Proteins, Cell Line, Cloning, Molecular, Exocytosis, Membrane Glycoproteins, Membrane Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Protein Binding, Recombinant Proteins, Synapses, R-SNARE Proteins, Qa-SNARE Proteins, Synaptosomal-Associated Protein 25, Synaptotagmins, Mice, Rats
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