Synaptotagmin-syntaxin interaction: The C2 domain as a Ca2+-dependent electrostatic switch

Xuguang Shao; Cai Li; Imma Fernandez; Xiangyang Zhang; Thomas C. Südhof; Jose Rizo-Rey

doi:10.1016/S0896-6273(01)80052-0

Synaptotagmin-syntaxin interaction: The C₂ domain as a Ca²⁺-dependent electrostatic switch

Xuguang Shao, Cai Li, Imma Fernandez, Xiangyang Zhang, Thomas C. Südhof, Jose Rizo-Rey

Research output: Contribution to journal › Article › peer-review

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Abstract

Synaptotagmin I is a synaptic vesicle protein that is thought to act as a Ca²⁺ sensor in neurotransmitter release. The first C₂ domain of synaptotagmin I (C₂A domain) contains a bipartite Ca²⁺-binding motif and interacts in a Ca²⁺-dependent manner with syntaxin, a central component of the membrane fusion complex. Analysis by nuclear magnetic resonance spectroscopy and site-directed mutagenesis shows that this interaction is mediated by the cooperative action of basic residues surrounding the Ca²⁺- binding sites of the C₂A domain and is driven by a change in the electrostatic potential of the C₂A domain induced by Ca²⁺ binding. A model is proposed whereby synaptotagmin acts as an electrostatic switch in Ca²⁺- triggered synaptic vesicle exocytosis, promoting a structural rearrangement in the fusion machinery that is effected by its interaction with syntaxin.

Original language	English (US)
Pages (from-to)	133-142
Number of pages	10
Journal	Neuron
Volume	18
Issue number	1
DOIs	https://doi.org/10.1016/S0896-6273(01)80052-0
State	Published - Jan 1997

ASJC Scopus subject areas

Neuroscience(all)

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10.1016/S0896-6273(01)80052-0

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title = "Synaptotagmin-syntaxin interaction: The C2 domain as a Ca2+-dependent electrostatic switch",

abstract = "Synaptotagmin I is a synaptic vesicle protein that is thought to act as a Ca2+ sensor in neurotransmitter release. The first C2 domain of synaptotagmin I (C2A domain) contains a bipartite Ca2+-binding motif and interacts in a Ca2+-dependent manner with syntaxin, a central component of the membrane fusion complex. Analysis by nuclear magnetic resonance spectroscopy and site-directed mutagenesis shows that this interaction is mediated by the cooperative action of basic residues surrounding the Ca2+- binding sites of the C2A domain and is driven by a change in the electrostatic potential of the C2A domain induced by Ca2+ binding. A model is proposed whereby synaptotagmin acts as an electrostatic switch in Ca2+- triggered synaptic vesicle exocytosis, promoting a structural rearrangement in the fusion machinery that is effected by its interaction with syntaxin.",

author = "Xuguang Shao and Cai Li and Imma Fernandez and Xiangyang Zhang and S{\"u}dhof, {Thomas C.} and Jose Rizo-Rey",

note = "Funding Information: Correspondence should be addressed to J. R. I. F. was a fellow from the Ministerio de Educacion y Ciencia of Spain. This work was supported by a grant from the Welch Foundation (J. R.), by a joint grant from the William Randolph Hearst Foundation and the United Cerebral Palsy Research and Educational Foundation (J. R.), and by National Institutes of Health grants R29 NS33731-01A1 (J. R.) and RO1-MH52804-01 (T. C. S.).",

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doi = "10.1016/S0896-6273(01)80052-0",

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T2 - The C2 domain as a Ca2+-dependent electrostatic switch

AU - Shao, Xuguang

AU - Li, Cai

AU - Fernandez, Imma

AU - Zhang, Xiangyang

AU - Südhof, Thomas C.

AU - Rizo-Rey, Jose

N1 - Funding Information: Correspondence should be addressed to J. R. I. F. was a fellow from the Ministerio de Educacion y Ciencia of Spain. This work was supported by a grant from the Welch Foundation (J. R.), by a joint grant from the William Randolph Hearst Foundation and the United Cerebral Palsy Research and Educational Foundation (J. R.), and by National Institutes of Health grants R29 NS33731-01A1 (J. R.) and RO1-MH52804-01 (T. C. S.).

PY - 1997/1

Y1 - 1997/1

N2 - Synaptotagmin I is a synaptic vesicle protein that is thought to act as a Ca2+ sensor in neurotransmitter release. The first C2 domain of synaptotagmin I (C2A domain) contains a bipartite Ca2+-binding motif and interacts in a Ca2+-dependent manner with syntaxin, a central component of the membrane fusion complex. Analysis by nuclear magnetic resonance spectroscopy and site-directed mutagenesis shows that this interaction is mediated by the cooperative action of basic residues surrounding the Ca2+- binding sites of the C2A domain and is driven by a change in the electrostatic potential of the C2A domain induced by Ca2+ binding. A model is proposed whereby synaptotagmin acts as an electrostatic switch in Ca2+- triggered synaptic vesicle exocytosis, promoting a structural rearrangement in the fusion machinery that is effected by its interaction with syntaxin.

AB - Synaptotagmin I is a synaptic vesicle protein that is thought to act as a Ca2+ sensor in neurotransmitter release. The first C2 domain of synaptotagmin I (C2A domain) contains a bipartite Ca2+-binding motif and interacts in a Ca2+-dependent manner with syntaxin, a central component of the membrane fusion complex. Analysis by nuclear magnetic resonance spectroscopy and site-directed mutagenesis shows that this interaction is mediated by the cooperative action of basic residues surrounding the Ca2+- binding sites of the C2A domain and is driven by a change in the electrostatic potential of the C2A domain induced by Ca2+ binding. A model is proposed whereby synaptotagmin acts as an electrostatic switch in Ca2+- triggered synaptic vesicle exocytosis, promoting a structural rearrangement in the fusion machinery that is effected by its interaction with syntaxin.

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Synaptotagmin-syntaxin interaction: The C₂ domain as a Ca²⁺-dependent electrostatic switch

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