GTP BINDING PROTEINS OF THE PRESYNAPTIC NERVE TERMINAL

突触传递是细胞间的主要细胞过程 大脑中神经元之间的通信。在过去的几年里，许多人 在调节神经递质释放的重要蛋白质中 识别和功能研究导致了一系列关于 囊泡对接、激活和释放的生化途径。尽管 在这一进展中，膜贩运方面的许多关键事件在 神经末梢还不清楚，许多蛋白质的作用仍然是 要下定决心。最近发现的两种哺乳动物蛋白质rsec6和rsec6 Rsec8，与酵母分泌重要基因的序列同源性。 这项提案将研究这些分子在 突触前递质释放。我们将测试特定的假设 Rsec6和rsec8分子与低分子的 重量GTP酶，或Rab蛋白，调节囊泡的早期特征 对接。此外，我们建议研究rsec6的本地化和 Rsec8分子，并表征它们与 分泌途径的其他组成部分。 这些研究有望进一步阐明其分子机制。 突触的神经递质分泌。参与其中的分子 递质释放可能是导致神经系统疾病的靶标。 神经系统的精神障碍。此外, 了解导致递质释放的生化途径可能会有一些 允许合理设计对治疗有用的治疗化合物 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.