SNAP-mediated protein-protein interactions essential for neurotransmitter release.
The constitutive fusion of transport vesicles with intracellular membranes requires soluble proteins called SNAPs. Certain presynaptic proteins implicated in synaptic vesicle exocytosis also bind SNAPs, suggesting that SNAPs participate in the calcium-regulated membrane fusion events mediating neurotransmitter release. 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.
Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710.
W M
WM
DeBello
V
V
O'Connor
T
T
Dresbach
S W
SW
Whiteheart
S S
SS
Wang
F E
FE
Schweizer
H
H
Betz
J E
JE
Rothman
G J
GJ
Augustine
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D006224:Cricetinae; D049832:Decapodiformes; D006056:Golgi Apparatus / Q000378:metabolism; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism*; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D013569:Synapses / Q000378:metabolism; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D008565:Membrane Proteins; D018377:Neurotransmitter Agents; D009842:Oligopeptides; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D033921:Vesicular Transport Proteins; D002118:Calcium