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Binding of synaptotagmin to the α-latrotoxin receptor implicates both in synaptic vesicle exocytosis

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Abstract

A VERTEBRATE neurotoxin, α-latrotoxin, from black widow spider venom causes synaptic vesicle exocytosis and neurotransmitter release from presynaptic nerve terminals11–4. Although the mechanism of action of α-latrotoxin is not known, it does require binding of α-latrotoxin to a high-affinity receptor on the presynaptic plasma membrane5. The α-latrotoxin receptor seems to be exclusively at the presynaptic plasmamembrane6. Here we report that the α-latrotoxin receptor specifically binds to a synaptic vesicle protein, synaptotagmin, and modulates its phosphorylation. Synaptotagmin is a synaptic vesicle-specific membrane protein that binds negatively charged phospholipids and contains two copies of a putative Ca2+-binding domain from protein kinase C (the C2-domain), suggesting a regulatory role in synaptic vesicle fusion7,8. Our findings suggest that a physiological role of the α-latrotoxin receptor may be the docking of synaptic vesicles at the active zone. The direct interaction of the α-latrotoxin receptor with a synaptic vesicle protein also suggests a mechanism of action for this toxin in causing neurotransmitter release.

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Author notes

  1. Thomas C. Südhof: To whom correspondence should be addressed

Authors and Affiliations

  1. Howard Hughes Medical Institute and Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas, 75235, USA

    Alexander G. Petrenko, Mark S. Perin, Yuri A. Ushkaryov, Martin Geppert & Thomas C. Südhof

  2. Shemyakin Institute of Bioorganic Chemistry, USSR Academy of Sciences, Moscow, 117871, USSR

    Alexander G. Petrenko & Bazbek A. Davletov

Authors
  1. Alexander G. Petrenko
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  2. Mark S. Perin
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  3. Bazbek A. Davletov
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  4. Yuri A. Ushkaryov
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  5. Martin Geppert
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  6. Thomas C. Südhof
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Petrenko, A., Perin, M., Davletov, B. et al. Binding of synaptotagmin to the α-latrotoxin receptor implicates both in synaptic vesicle exocytosis. Nature 353, 65–68 (1991). https://doi.org/10.1038/353065a0

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  • DOI: https://doi.org/10.1038/353065a0

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