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The Journal of Neuroscience, February 15, 2002, 22(4):1266-1272

The Core Membrane Fusion Complex Governs the Probability of Synaptic Vesicle Fusion But Not Transmitter Release Kinetics

Michael F. A. Finley1, 2, Sejal M. Patel1, Daniel V. Madison2, and Richard H. Scheller1, 2

1 Howard Hughes Medical Institute and 2 Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305

Synaptic vesicle fusion is driven by the formation of a four-helical bundle composed of soluble N-ethylmaleimide sensitive factor (NSF) attachment protein receptors (SNAREs). Exactly how the structural interactions that lead to the formation of this complex relate to neurotransmitter release is not well understood. To address this question, we used a strategy to "rescue" synaptic transmission after proteolytic cleavage of the synaptosome-associated protein of 25 kDa (SNAP-25) by botulinum neurotoxin E (BoNtE). Transfection of CA3 hippocampal pyramidal cells with BoNtE-resistant SNAP-25 restored synaptic transmission. Additional mutations that alter the interaction between SNAP-25 C-terminal coil and the other SNARE coils dramatically reduce transmitter release probability but leave the kinetics of synaptic responses unaltered. These data indicate that at synapses, SNARE interactions are necessary for fusion but are not the rate-limiting step of neurotransmission.

Key words: soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptors (SNAREs); SNAP-25; botulinum neurotoxin E (BoNtE); hippocampus; synaptic transmission; vesicle fusion


Copyright © 2002 Society for Neuroscience  0270-6474/02/2241266-07$05.00/0


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