Binding of the synaptic vesicle v-SNARE, synaptotagmin, to the plasma membrane t-SNARE, SNAP-25, can explain docked vesicles at neurotoxin-treated synapses

Binding of the synaptic vesicle v-SNARE, synaptotagmin, to the plasma membrane t-SNARE, SNAP-25, can explain docked vesicles at neurotoxin-treated synapses

Cellular Biochemistry and Biophysics Program, Memorial Sloan–Kettering Cancer Center, New York, NY 10021

Abstract

Neurotransmitter release requires the specific docking of synaptic vesicles to the presynaptic plasma membrane followed by a calcium-triggered fusion event. Herein we report a previously unsuspected interaction of the synaptic vesicle protein and likely calcium sensor synaptotagmin with the plasma membrane t-SNARE SNAP-25. This interaction appears to resolve the apparent paradox that synaptic vesicles are capable of docking even when VAMP (vesicle-associated membrane protein) or syntaxin is cleaved or deleted and suggests that two species of v-SNAREs (VAMP and synaptotagmin) and two species of t-SNAREs (SNAP-25 and syntaxin) interact to functionally dock synaptic vesicles.

Footnotes

↵ * To whom reprint requests should be addressed. e-mail: t-sollner{at}ski.mskcc.org.
James E. Rothman
Abbreviations: SNAP-25, synaptosome-associated protein of 25 kDa; SNARE, SNAP receptor; v-SNARE, vesicle SNARE; t-SNARE, target-localized SNARE; tagmin, synaptotagmin I; VAMP, vesicle-associated membrane protein; GST, glutathione S-transferase; NSF, N-ethylmaleimide-sensitive fusion protein; SNAP, soluble NSF attachment protein; BoNT/A, botulinum neurotoxin serotype A; BoNT/E, botulinum neurotoxin serotype E.