A NEURONAL SEC1 HOMOLOG REGULATES NEUROTRANSMITTER RELEASE AT THE SQUID GIANT SYNAPSE

Citation
T. Dresbach et al., A NEURONAL SEC1 HOMOLOG REGULATES NEUROTRANSMITTER RELEASE AT THE SQUID GIANT SYNAPSE, The Journal of neuroscience, 18(8), 1998, pp. 2923-2932
Citations number
48
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
02706474
Volume
18
Issue
8
Year of publication
1998
Pages
2923 - 2932
Database
ISI
SICI code
0270-6474(1998)18:8<2923:ANSHRN>2.0.ZU;2-#
Abstract
Sec1-related proteins are essential for membrane fusion at distinct st ages of the constitutive and regulated secretory pathways in eukaryoti c cells, Studies of neuronal isoforms of the Sec1 protein family have yielded evidence for both positive and negative regulatory functions o f these proteins in neurotransmitter release, Here, we have identified a squid neuronal homolog (s-Sec1) of Sec1 proteins and examined its f unction in neurotransmitter release at the squid giant synapse, Microi njection of s-Sec1 into the presynaptic terminal of the giant synapse inhibited evoked neurotransmitter release, but this effect was prevent ed by coinjecting the cytoplasmic domain of squid syntaxin (s-syntaxin ), one of the binding partners of s-Sec1, A 24 amino acid peptide frag ment of s-Sec1, which inhibited the binding of s-Sec1 to s-syntaxin in vitro, completely blocked release, suggesting an essential function o f the s-Sec1/s-syntaxin interaction in transmitter release. Electron m icroscopy showed that injection of s-Sec1 did not change the spatial d istribution of synaptic vesicles at presynaptic release sites (''activ e zones''), whereas the inhibitory peptide increased the number of doc ked vesicles, These distinct morphological effects lead us to conclude that Sec1 proteins function at different stages of synaptic vesicle e xocytosis, and that an interaction of s-Sec1 with syntaxin-at a stage blocked by the peptide-is necessary for docked vesicles to fuse.