Ca2+-Dependent Synaptotagmin Binding to SNAP-25 Is Essential for Ca2+-Triggered Exocytosis

@article{Zhang2002Ca2DependentSB,
  title={Ca2+-Dependent Synaptotagmin Binding to SNAP-25 Is Essential for Ca2+-Triggered Exocytosis},
  author={Xiaodong Zhang and Mindy J. Kim-Miller and Mitsunori Fukuda and Judith A. Kowalchyk and Thomas F. J. Martin},
  journal={Neuron},
  year={2002},
  volume={34},
  pages={599-611}
}
Synaptotagmin is a proposed Ca2+ sensor on the vesicle for regulated exocytosis and exhibits Ca2+-dependent binding to phospholipids, syntaxin, and SNAP-25 in vitro, but the mechanism by which Ca2+ triggers membrane fusion is uncertain. Previous studies suggested that SNAP-25 plays a role in the Ca2+ regulation of secretion. We found that synaptotagmins I and IX associate with SNAP-25 during Ca2+-dependent exocytosis in PC12 cells, and we identified C-terminal amino acids in SNAP-25 (Asp179… Expand
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TLDR
Results provide direct evidence that Ca(2+)-dependent SNARE binding by synaptotagmin is essential for Ca( 2+)-triggered vesicle exocytosis and that Ca (2+)+)-dependent membrane binding by itself is insufficient to trigger fusion. Expand
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Synaptotagmin is a synaptic vesicle membrane protein that is postulated to function as a calcium (Ca2+) sensor for neurotransmitter release. This protein contains two Ca2+-binding domains (C2A, C2B)Expand
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TLDR
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TLDR
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Augmenting neurotransmitter release by enhancing the apparent Ca2+ affinity of synaptotagmin 1.
TLDR
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TLDR
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TLDR
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Fusion Pore Dynamics Are Regulated by Synaptotagmin•t-SNARE Interactions
TLDR
The final step of Ca2+-triggered exocytosis is regulated, at least in part, by direct contacts between syt and SNAP-25/syntaxin. Expand
Calcium Binding by Synaptotagmin's C2A Domain is an Essential Element of the Electrostatic Switch That Triggers Synchronous Synaptic Transmission
TLDR
It is shown that the major function of Ca2+ binding to C2A is to neutralize the negative charge of the pocket, thereby unleashing the fusion-stimulating activity of synaptotagmin. Expand
Synaptotagmin Interaction with SNAP-25 Governs Vesicle Docking, Priming, and Fusion Triggering
TLDR
It is demonstrated that the postulated central binding domain surrounding layer zero covers both SNARE motifs of SNAP-25 and is essential for vesicle docking, priming, and fast fusion-triggering, suggesting that synaptotagmin-1 × SNARE interactions are not only required for multiple mechanistic steps en route to fusion but also underlie the developmental control of the releasable vesicles pool. Expand
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TLDR
It is suggested that an essential role for the C terminus of SNAP25 in regulated exocytosis is to mediate Ca2+-dependent interactions between synaptotagmin and SNARE protein complexes. Expand
Ca2+ Regulates the Interaction between Synaptotagmin and Syntaxin 1 (*)
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It is reported that Ca2+ increases the affinity between synaptotagmin and syntaxin 1, a component of the synaptic fusion apparatus, and proposed that this interaction constitutes an essential step in excitation-secretion coupling. Expand
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TLDR
The data indicate that the Ca2+-driven clustering of the C2B domain of synaptotagmin is an essential step in excitation-secretion coupling, and it is proposed that clustering may regulate the opening or dilation of the exocytotic fusion pore. Expand
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Calcium dependence of neurotransmitter release and rate of spontaneous vesicle fusions are altered in Drosophila synaptotagmin mutants.
TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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