Disruption of syntaxin-mediated protein interactions blocks neurotransmitter secretion.
The membrane protein syntaxin participates in several protein-protein interactions that have been implicated in neurotransmitter release. To probe the physiological importance of these interactions, we microinjected into the squid giant presynaptic terminal botulinum toxin C1, which cleaves syntaxin, and the H3 domain of syntaxin, which mediates binding to other proteins. Both reagents inhibited synaptic transmission yet did not affect the number or distribution of synaptic vesicles at the presynaptic active zone. Recombinant H3 domain inhibited the interactions between syntaxin and SNAP-25 that underlie the formation of stable SNARE complexes in vitro. These data support the notion that syntaxin-mediated SNARE complexes are necessary for docked synaptic vesicles to fuse.
O'Connor
V
V
Department of Neurochemistry, Max-Planck-Institute for Brain Research, 60528 Frankfurt, Germany.
Heuss
C
C
De Bello
W M
WM
Dresbach
T
T
Charlton
M P
MP
Hunt
J H
JH
Pellegrini
L L
LL
Hodel
A
A
Burger
M M
MM
Betz
H
H
Augustine
G J
GJ
Schäfer
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D003001:Cloning, Molecular; D049832:Decapodiformes / Q000235:genetics*; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects / Q000648:ultrastructure; D011485:Protein Binding / Q000187:drug effects; D050765:Qa-SNARE Proteins; D050600:SNARE Proteins; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D050825:Synaptosomal-Associated Protein 25; D033921:Vesicular Transport Proteins
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D050765:Qa-SNARE Proteins; D050600:SNARE Proteins; D050825:Synaptosomal-Associated Protein 25; D033921:Vesicular Transport Proteins; D001905:Botulinum Toxins; C096324:botulinum toxin type C