GTP BINDING PROTEINS OF THE PRESYNAPTIC NERVE TERMINAL

突触传递是用于细胞间传递的主要细胞过程。 大脑中神经元之间的交流。 在过去的几年里，许多 在调节神经递质释放中起重要作用的蛋白质 已确定的和功能的研究，导致了一系列的建议， 囊泡对接、激活和释放的生化途径。 尽管 在这一进展中，许多关键事件在膜内运输 神经末梢还不清楚，许多蛋白质的作用仍然是 下定决心。 两个最近鉴定的哺乳动物蛋白，rsec6和 rsec8，与对分泌重要的酵母基因共享序列同源性。 该提案将研究这些分子在以下方面的潜在作用： 突触前递质释放 我们将检验以下特定假设： Rsec6和Rsec8分子与低分子量的 重GT3或Rab蛋白，以调节囊泡的早期方面 对接 此外，我们建议研究rsec6的本地化， rsec8分子，并表征其与 分泌途径的其他成分。 这些研究有望进一步阐明 神经传递素在突触处的分泌。 参与的分子 神经递质的释放可能是导致神经系统疾病的目标， 和中枢神经系统的精神障碍。 此外，本发明还提供了一种方法， 了解导致递质释放的生化途径， 这些方法允许合理设计可用于治疗 神经系统疾病。

Synaptic transmission is the major cellular process used for intercellular communication between neurons in the brain. In the last several years many of the proteins important in mediating neurotransmitter release have been identified and functional studies have led to a series of proposals for the biochemical pathway of vesicle docking, activation and release. In spite of this progress, many critical events in membrane trafficking within the nerve terminal are not understood and the roles of many proteins remain to be determined. Two recently identified mammalian proteins, rsec6 and rsec8, share sequence homology =with yeast genes important for secretion. This proposal will investigate the potential roles of these molecules in presynaptic transmitter release. We will test the specific hypothesis that the rsec6 and rsec8 molecules function in conjunction with a low-molecular weight GTPase, or Rab protein, to regulate early aspects of vesicle docking. Further, we propose to study the localization of the rsec6 and rsec8 molecules and to characterize their biochemical interactions with other components of the secretory pathway. These studies are expected to further elucidate the molecular mechanisms of neurotransmitter secretion at the synapse. the molecules involved in transmitter release are likely targets for diseases that lead to neurologic and psychiatric disorders of athe nervous system. In addition, understanding biochemical pathway leading to transmitter release may some day allow the rational design of therapeutic compounds useful in treating diseases of the nervous system.