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SNAP-mediated protein–protein interactions essential for neurotransmitter release

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Abstract

THE constitutive fusion of transport vesicles with intracellular membranes requires soluble proteins called SNAPs1. Certain pre-synaptic proteins2–1 implicated in synaptic vesicle exocytosis5 also bind SNAPs, suggesting that SNAPs participate in the calcium-regulated membrane fusion events mediating neurotransmitter release6,7. Here we show that injection of recombinant SNAPs into the giant synapse of squid enhances transmitter release. Conversely, injection of peptides designed to mimic the sites at which SNAP interacts with its binding partners inhibits transmitter release downstream of synaptic vesicle docking. A SNAP-dependent protein complex must therefore mediate transmitter release, showing that transmitter release shares a common molecular mechanism with constitutive membrane fusion.

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Author notes

  1. S. W. Whiteheart

    Present address: Department of Biochemistry, University of Kentucky College of Medicine, Chandler Medical Center, 800 Rose Street, Lexington, KY, 40536-0084, USA

  2. W. M. DeBello: To whom correspondence should be addressed at Duke University.

Authors and Affiliations

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

    W. M. DeBello, S. S.-H. Wang, F. E. Schweizer & G. J. Augustine

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

    W. M. DeBello, T. Dresbach, S. S.-H. Wang, F. E. Schweizer, H Bertz & G. J. Augustine

  3. Department of Neurochemistry, Max-Planck-Institute for Brain Research, 60528, Frankfurt, Germany

    V. O'Connor, T. Dresbach & H Bertz

  4. Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York, 10021, USA

    S. W. Whiteheart & J. E. Rothman

Authors
  1. W. M. DeBello
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  2. V. O'Connor
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  3. T. Dresbach
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  5. S. S.-H. Wang
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  6. F. E. Schweizer
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  7. H Bertz
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  8. J. E. Rothman
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  9. G. J. Augustine
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DeBello, W., O'Connor, V., Dresbach, T. et al. SNAP-mediated protein–protein interactions essential for neurotransmitter release. Nature 373, 626–630 (1995). https://doi.org/10.1038/373626a0

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  • DOI: https://doi.org/10.1038/373626a0

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