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

长时程增强（LTP）被认为是理解记忆形成和储存的细胞和分子机制的重要关键。大量研究表明，LTP的重要机制涉及突触前细胞释放谷氨酸和突触后谷氨酸受体反应性的改变。包括谷氨酸在内的神经递质是通过突触囊泡胞吐作用释放的，胞吐作用受多种成分的调节。Rab 3A小G蛋白和Doc 2已被证明是调节Ca^2+依赖性突触囊泡胞吐的调节组分。Rab 3A在GDP结合的非活性形式和GTP结合的活性形式之间循环，并在突触前神经末梢的胞质溶胶与突触囊泡的膜和突触前质膜之间易位。活化和转运受B调节 关于我们 3个调节子（RabGDI α、Rab 3 GAP、Rab 3 GEP）。我们对Rab GDIα缺陷小鼠的研究表明，这种蛋白对基础神经递质的释放不是必需的，但调节突触可塑性。相比之下，Rab 3 GEP缺陷小鼠表现出更严重的表型，出生后立即死于呼吸功能不全。我们分离出一种新的蛋白质，该蛋白质与Rab 3 GEP和GAP通过其各自的抗体从大鼠脑的粗突触囊泡组分中共免疫沉淀。这种蛋白被命名为rabconnectin-3，至少结合Rab 3 GEP和GAP。Doc 2与Munc 13以二酰基甘油依赖性方式相互作用，并且这种相互作用参与对接过程。我们对Doc 2缺陷小鼠的研究表明，这种蛋白质不是基础神经递质释放所必需的，但调节突触可塑性。对Rab 3A和Doc 2系统的进一步研究对于理解突触可塑性的分子机制是必要的，这可能是学习和记忆的基础。

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