Nature 373, 626 - 630 (16 February 1995); doi:10.1038/373626a0

SNAP-mediated protein–protein interactions essential for neurotransmitter release

W. M. DeBello^*†‡, V. O'Connor^§, T. Dresbach^†§, S. W. Whiteheart^¶, S. S.-H. Wang^*†, F. E. Schweizer^*†, H Bertz^†§, J. E. Rothman & G. J. Augustine^*†

^*Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA
^†Marine Biological Laboratory, Woods Hole, Massachusetts 02543, USA
^§Department of Neurochemistry, Max-Planck-Institute for Brain Research, 60528 Frankfurt, Germany
Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
^‡To whom correspondence should be addressed at Duke University.
^¶Present address: Department of Biochemistry, University of Kentucky College of Medicine, Chandler Medical Center, 800 Rose Street, Lexington, KY 40536-0084, USA.

THE constitutive fusion of transport vesicles with intracellular membranes requires soluble proteins called SNAPs¹. Certain pre-synaptic proteins^2–1 implicated in synaptic vesicle exocytosis⁵ also bind SNAPs, suggesting that SNAPs participate in the calcium-regulated membrane fusion events mediating neurotransmitter release^6,7. 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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