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Inhibition of neurotransmitter release by C2-domain peptides implicates synaptotagmin in exocytosis

Nature volume 363, pages 163–165 (1993)Cite this article

Abstract

NEUROTRANSMITTER release is triggered by Ca2+ ions binding to an unknown Ca2+ receptor within presynaptic terminals1,2. Synaptotagmin, a Ca2+-binding protein of synaptic and other secretory vesicles3, has been proposed to mediate vesicle–plasma membrane interactions during neurotransmitter release4–9. Here we test this hypothesis using the giant synapse of the squid Loligo pealei, which because of its unusually large size and well established physiology is uniquely suited for dissecting presynaptic events10. We find that injection of peptides from the C2 domains of synaptotagmin into squid giant presynaptic terminals rapidly and reversibly inhibits neurotransmitter release. Our data are consistent with these peptides competitively blocking release after synaptic vesicle docking and indicate that Ca2+ probably initiates neurotransmitter release by regulating the interaction of synaptotagmin with an acceptor protein.

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Authors and Affiliations

  1. Marine Biological Laboratory, Woods Hole, Massachusetts, 02543, USA

    Kurt Bommert, Milton P. Charlton, William M. DeBello, Gilbert J. Chin & George J. Augustine

  2. Department of Neurochemistry, Max-Planck Institute for Brain Research, Deutschordenstrasse 46, 6000, Frankfurt, 71, Germany

    Kurt Bommert & Heinrich Betz

  3. Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada

    Milton P. Charlton

  4. Department of Neurobiology, Duke University Medical Center, Durham, North Carolina, 27710, USA

    William M. DeBello & George J. Augustine

  5. Laboratory of Developmental Neurobiology, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Gilbert J. Chin

Authors
  1. Kurt Bommert
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  2. Milton P. Charlton
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  3. William M. DeBello
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  4. Gilbert J. Chin
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  5. Heinrich Betz
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  6. George J. Augustine
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Bommert, K., Charlton, M., DeBello, W. et al. Inhibition of neurotransmitter release by C2-domain peptides implicates synaptotagmin in exocytosis. Nature 363, 163–165 (1993). https://doi.org/10.1038/363163a0

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