Molecular mechanism of synatic vesicle exocytosis-Role of vesicle transport in synaptic plasticity

突触小泡胞吐作用的分子机制-小泡运输在突触可塑性中的作用

基本信息

批准号：
10215204
负责人：
SASAKI Takuya
金额：
$ 22.08万
依托单位：
The University of Tokushima Graduate School of Medicine (2000-2001)Osaka University (1998-1999)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2001
项目状态：
已结题

项目摘要

Long-term potentiation (LTP) is believed to provide an important key to understanding the cellular and molecular mechanisms by which memories are formed and stored. Numerous studies strongly suggest that important mechanisms underlying LTP involves alternations in the release of glutamate from the presynaptic cells and the resposiveness of the postsynaptic glutamate receptors. Neurotransmitters including glutamate are released by synaptic vesicle exocytosis which is regulated by many components They are classified into essential and modulatory ones for neurotransmitter release. Rab3A small G protein and Doc2 have been shown to be modulatory components which regulate Ca^<2+>-dependent synaptic vesicle exocytosis. Rab3A cycles between the GDP-bound inactive form and the GTP-bound active form and translocates between the cytosol of the presynaptic nerve terminal and the membranes of synaptic vesicles and the presynaptic plasma membrane. The activation and the translocation are regulated b … More y three regulators (Rab GDIα, Rab3 GAP, Rab3 GEP). Our studies on Rab GDIα-deficient mice indicate that this protein is not essential for basal neurotransmitter release but regulates synaptic plasticity. In contrast, Rab3 GEP-deficient mice show much more severe phenotypes and die immediately after birth due to respiratory insufficiency. We isolated a novel protein that was co-immunoprecipitated with Rab3 GEP and GAP by their respective antibodies from the crude synaptic vesicle fraction of rat brain. The protein, named rabconnectin-3, bound at least both Rab3 GEP and GAP. Doc2 interacts with Munc13 in a diacylglycerol-dependent manner, and this interaction is involved in the docking process. Our studies on Doc2-deficient mice indicate that this protein is not essential for basal neurotransmitter release but regulates synaptic plasticity Further studies on the Rab3A and Doc2 systems are necessary for understanding of the molecular mechanism of synaptic plasticity, which may underlie learning and memory Less

长期增强（LTP）是理解细胞和分子记忆的重要关键。被归类为神经递质释放的必不可少的和调节性的。突触前神经末端的细胞质和突触囊泡的膜和突触前的质质膜。基础神经递质释放，但会调节突触的塑性。大脑。必不可少的释放器释放，但调节系统是突触塑性分子机制的必要条件，这可能是学习学习和记忆的基础