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Evidence for synaptotagmin as an inhibitory clamp on synaptic vesicle release in Aplysia neurons.

ABSTRACT: While previous studies have demonstrated that synaptotagmin plays an essential role in evoked neurotransmitter release, it has been difficult to determine whether it acts to facilitate or inhibit release. To address this question, we used acute genetic manipulations to alter the expression of synaptotagmin in Aplysia neurons. Transient overexpression of synaptotagmin in acutely dissected cholinergic neurons and in cultured glutaminergic neurons decreased the amplitude of the excitatory postsynaptic potential (EPSP) by 32% and 26%, respectively. In contrast, treatment of cultured presynaptic neurons with synaptotagmin antisense oligonucleotides increased the amplitude of the EPSP by 50-75%. These results are consistent with a role of synaptotagmin as an inhibitor of release.

SUBMITTER: Martin KC

PROVIDER: S-EPMC40621 | biostudies-other | 1995 Nov

REPOSITORIES: biostudies-other

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Evidence for synaptotagmin as an inhibitory clamp on synaptic vesicle release in Aplysia neurons.

Martin K C KC Hu Y Y Armitage B A BA Siegelbaum S A SA Kandel E R ER Kaang B K BK

Proceedings of the National Academy of Sciences of the United States of America 19951101 24

While previous studies have demonstrated that synaptotagmin plays an essential role in evoked neurotransmitter release, it has been difficult to determine whether it acts to facilitate or inhibit release. To address this question, we used acute genetic manipulations to alter the expression of synaptotagmin in Aplysia neurons. Transient overexpression of synaptotagmin in acutely dissected cholinergic neurons and in cultured glutaminergic neurons decreased the amplitude of the excitatory postsynap ...[more]

PMID: 7479985

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Project description:Synaptotagmin-1 (SYT1) is a synaptic vesicle resident protein that interacts via its C2 domain with anionic lipids from the plasma membrane in a calcium-dependent manner to efficiently trigger rapid neurotransmitter (NT) release. In addition, SYT1 acts as a negative regulator of spontaneous NT release and regulates synaptic vesicle (SV) priming. How these functions relate to each other mechanistically and what role other synaptotagmin (SYT) isoforms play in supporting and complementing the role of SYT1 is still under intensive investigation. In this work, we analyzed three putative functions of SYT1 in exocytosis by systematically varying its expression in autaptic hippocampal glutamatergic neurons from mice of either sex. We find that regulation of release probability is most sensitive to variation of expression levels, whereas its impact on vesicle priming is least sensitive. Also, loss of SYT1 phenotypes on spontaneous release and vesicle priming is compensated in less mature synaptic cultures by redundant support from SYT7. Overall, our data help in resolving some controversies in SYT1 functions in exocytosis and in our understanding of how SYT1 contributes to the pathophysiology underlying SYT1-related human neurologic disorders.SIGNIFICANCE STATEMENT Our work clarifies the functions of SYT1 protein in synaptic vesicle priming and spontaneous and calcium-evoked neurotransmitter release and analyzes whether these occur at different stages of synaptic responses by examining their relative sensitivity to protein concentration at the synaptic terminal. We demonstrate that these synaptic functions are unequally sensitive to both protein levels and neuronal stage, indicating that they operate under distinct molecular mechanisms. Furthermore, we analyze how these functions are modulated by another synaptotagmin isoform expression. We show that to understand the phenotype displayed by SYT1 knock-out neurons (Syt1 -/-) is necessary to consider the interplay between SYT1 and SYT7 molecules at the presynaptic terminal.

Dataset Information

Evidence for synaptotagmin as an inhibitory clamp on synaptic vesicle release in Aplysia neurons.

Publications

Evidence for synaptotagmin as an inhibitory clamp on synaptic vesicle release in Aplysia neurons.

Similar Datasets

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