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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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