CONANTOKINS AND NMDA RECEPTORS

我们建议研究NMDA受体(主要类型之一 兴奋性氨基酸受体)使用Conus多肽，特别是 康纳托金。Conantokins是已知的唯一一种能够 影响NMDA受体的功能。这些多肽都很小(~20 氨基酸)，是化学合成的，含有一种不同寻常的 氨基酸，伽玛-羧基谷氨酸。康纳托金被发现了 因为它们会使幼鼠处于类似睡眠的状态，但矛盾的是， 在成熟的小鼠中，一种过度活跃的状态，特征是爬上一个快速的 相反，观察到了跑步综合症。该项目的长期目标 是在分子水平上阐明刀豆素是如何与 它们的受体靶标来产生这些行为效应。 来自我们实验室的初步数据表明，Conantokins 与由几个亚单位组成的受体复合体相互作用 不同的大众。其中一个推定的亚基与 NMDA最近的表达克隆数据预期的mW范围 受体。这个受体复合体将被提纯和鉴定。在……里面 此外，由于引起显著的发育症状 通过这些多肽，受体发生发育转换的可能性 我们将探索子类型。

We propose to investigate the NMDA receptor (one of the major types of excitatory amino acid receptors) using Conus peptides, in particular the conantokins. The conantokins are the only peptide ligands known which affect the function of the NMDA receptor. These peptides are small (~20 amino acids), have been chemically synthesized and contain an unusual amino acid, gamma-carboxyglutamate. The conantokins were discovered because they induce a sleep-like state in young mice, but paradoxically, in mature mice, a hyperactive state characterized by climbing a rapid running syndrome is observed instead. A long-range goal of the project is to elucidate at the molecular level how conantokins interact with their receptor targets to produce these behavioral effects. Preliminary data from our laboratories indicate that the conantokins interact with a receptor complex composed of several subunits with differing MWs. One of the putative subunits is not inconsistent with the MW range expected from recent expression cloning data for the NMDA receptor. This receptor complex will be purified and characterized. In addition, because of the striking developmental symptomatology induced by these peptides, the possibility of developmental switching in receptor subtypes will be explored.