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The Journal of Neuroscience, April 15, 1998, 18(8):2923-2932
A Neuronal Sec1 Homolog Regulates Neurotransmitter Release at the
Squid Giant Synapse
T.
Dresbach1, 3,
M. E.
Burns2, 3,
V.
O'Connor1,
W. M.
DeBello2, 3,
H.
Betz1, and
G. J.
Augustine2, 3
1 Department of Neurochemistry, Max-Planck-Institute
for Brain Research, 60528 Frankfurt, Germany, 2 Department
of Neurobiology, Duke University Medical Center, Durham, North Carolina
27710, and 3 Marine Biological Laboratory, Woods Hole,
Massachusetts 02543
Sec1-related proteins are essential for membrane fusion at distinct
stages of the constitutive and regulated secretory pathways in
eukaryotic cells. Studies of neuronal isoforms of the Sec1 protein
family have yielded evidence for both positive and negative regulatory
functions of these proteins in neurotransmitter release. Here, we have
identified a squid neuronal homolog (s-Sec1) of Sec1 proteins and
examined its function in neurotransmitter release at the squid giant
synapse. Microinjection of s-Sec1 into the presynaptic terminal of the
giant synapse inhibited evoked neurotransmitter release, but this
effect was prevented by coinjecting the cytoplasmic domain of squid
syntaxin (s-syntaxin), one of the binding partners of s-Sec1. A 24 amino acid peptide fragment of s-Sec1, which inhibited the binding of
s-Sec1 to s-syntaxin in vitro, completely blocked release, suggesting an essential function of the s-Sec1/s-syntaxin interaction in transmitter release. Electron microscopy showed that
injection of s-Sec1 did not change the spatial distribution of synaptic
vesicles at presynaptic release sites ("active zones"), whereas the
inhibitory peptide increased the number of docked vesicles. These
distinct morphological effects lead us to conclude that Sec1 proteins
function at different stages of synaptic vesicle exocytosis, and that
an interaction of s-Sec1 with syntaxin at a stage blocked by the
peptideis necessary for docked vesicles to fuse.
Key words:
active zone; microinjection; neurotransmitter release; Sec1 proteins; squid giant synapse; syntaxin
Copyright © 1998 Society for Neuroscience 0270-6474/98/1882923-10$05.00/0
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