某些天然毒素能以突触为靶标发挥作用，因而可作为分子工具使用。研究它们的功能和作用机理不仅可以加深对其本身的了解，而且可以帮助解析突触传递的分子机制。突触结合蛋白（Syt）和Rab3蛋白在突触传递调节中起关键作用，Rab3发挥调节作用时涉及一个Rab3循环。我们的前期工作首次证明Rab3A能通过与Syt I的直接互作调节囊泡的融合和多巴胺释放；在研究间斑寇蛛卵粒毒素-VI时，发现该毒素能促进PC12细胞多巴胺的释放，能经Syt I介导进入PC12细胞质与Rab3循环及相关蛋白（酶）作用，并可进入细胞核与转录有关的酶和调节因子作用。本项目拟在前期工作基础上，探究间斑寇蛛卵粒毒素-VI进入PC12细胞的过程与分子基础、阐明其影响多巴胺代谢与释放的分子机理，并为研究突触传递调控机制积累新的实验资料，为揭示间斑寇蛛卵粒毒素-VI在药理学研究和相关疾病的治疗等方面的潜在意义奠定初步基础。

Some natural toxins target the synapse and thus can be used as molecular tools. Investigation of their functions and action mechanism not only deepens our understanding of the toxins themselves, but also helps to dissect the molecular mechanism for regulation of synaptic transmission. Synaptotagmin and Rab3 play key roles in the regulation of synaptic transmission, and the regulatory action of Rab3 involves a Rab3 cycle. Our previous work for the first time demonstrated that Rab3A could regulate the vesicle fusion and dopamine release through direct interaction with synaptotagmin I; when the Latroeggtoxin-VI,a peptide toxin from the eggs of Latrodectus spider, was preliminarily investigated,the toxin was found to be able to promote dopamine release from PC12 cells, enter the cells via synaptotagmin I mediation to interact with Rab3 cycle and related proteins (enzymes), and enter the nucleus to interact with the transcription-related enzymes and regulatory factors. The present project will, on the basis of our previous work, probe into the process and molecular basis for Latroeggtoxin-VI to enter the PC12 cells ,not only revealing molecular mechanism underlying the effect of Latroeggtoxin-VI on the metabolism and release of dopamine,but also accumulating new experimental data for elucidating the regulatory mechanism of synaptic transmission, and establishing preliminary foundation for probing the potential of the toxin in the pharmacological research and the treatment of related diseases.