Molecular composition of transmitter release site and the mechanism of synaptic vesicle tethering

递质释放位点的分子组成及突触小泡束缚机制

基本信息

批准号：
12680747
负责人：
ABE Teruo
金额：
$ 2.24万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680747/
关键词：
transmitter release synaptic plasticity synaptic vesicle アクティブ・ゾーン

项目摘要

Recent studies have paved the way for the elucidation of the molecular mechanisms of neurotransmitter release. However, many aspects of the molecular composition and synaptic vesicle tethering mechanisms of the release site remain unsolved. In this research, we first studied the mechanism of action of the cytosolic protein synaphin in the release mechanisms. By injecting a peptide that constitute the synaphin binding site to syntaxin into the squid giant presynaptic terminal, we have shown that synaphin is essential for the fast release of neurotransmitter molecules. Our results suggest that the protein act by facilitating oligomerization of SNARE complexes. Synaphin probably acts just before fusion.The study on mGluR7 binding proteins is still underway. We have not yet succeeded in obtaining full-length cDNA clones for these proteins. The mRNAs for these proteins are probably very liable to degradation.To understand the mechanisms for synaptic vesicle localization at the release site at the internal surface of the plasma membrane in the nerve terminal we have used the neuromuscular junction of Drosophila larva. Our findings indicate that unlike the reserve pool of synaptic vesicles which involves the synaptic vesicle protein synapsin, the cytoskeletal protein tubulin is important for the formation of the readily releasable pool. The dynamic movement of tubulin structures in the nerve terminal was unambiguously demonstrated by immunohistochemical staining. Our results suggest an important role for microtubules in the nerve terminal.

最近的研究为阐明神经递质释放的分子机制铺平了道路。然而，释放位点的分子组成和突触小泡束缚机制的许多方面仍未解决。在本研究中，我们首先研究了胞浆蛋白突触蛋白在释放机制中的作用机制。通过将构成突触蛋白与突触蛋白结合位点的肽注射到鱿鱼巨型突触前末端，我们发现突触蛋白对于神经递质分子的快速释放至关重要。我们的结果表明该蛋白质通过促进 SNARE 复合物的寡聚化发挥作用。突触蛋白可能在融合之前发挥作用。对 mGluR7 结合蛋白的研究仍在进行中。我们尚未成功获得这些蛋白质的全长 cDNA 克隆。这些蛋白质的 mRNA 可能很容易降解。为了了解突触小泡定位在神经末梢质膜内表面释放位点的机制，我们使用了果蝇幼虫的神经肌肉接头。我们的研究结果表明，与涉及突触小泡蛋白突触蛋白的突触小泡储备池不同，细胞骨架蛋白微管蛋白对于易于释放池的形成非常重要。免疫组织化学染色明确证明了神经末梢微管蛋白结构的动态运动。我们的结果表明微管在神经末梢中发挥着重要作用。