ORGANIZATION OF ACTIVE ZONE WITHIN PRESYNAPTIC TERMINALS ON HIPPOCAMPAL NEURONS

在神经系统的发育过程中，许多细胞 包括细胞增殖、细胞分化、细胞增殖和细胞分化的过程 粘附、细胞迁移和细胞死亡是正确的细胞生长所必需的。 形成神经结构，并获得功能和 它们之间的可复制连接。 在神经系统中， 这些细胞过程被证明是由 通过生长因子及其受体。 受体 通过其酪氨酸激酶激活其配体后的反应 胞质尾区。 这类生长因子/受体的实例 对是NGF/trk、BDNF/trkB和NT 3/trkC。 一个尚未定性的 受体Tyro-3，属于这一类，是我们的主题， study. 这个项目的总体目标是了解一些 功能，主要是在细胞粘附和识别信号 受酪氨酸激酶Tyro-3影响的转导途径。 这 受体具有两个免疫球蛋白样重复序列和两个纤连蛋白 III型重复在其细胞外部分和细胞内 功能性酪氨酸激酶结构域，显示磷酸化后 结合其已知配体气体-6。 康贝特人将以 Tyro-3在海马中的超微结构定位，以 确定Tyro-3在突触发生和突触形成中可能作用 可塑性 初步数据表明，Tyro-3蛋白和 mRNA优先定位于CA 1的树突层 神经元 这种结构已被证明是至关重要的 阿尔茨海默病患者短时记忆建立及其影响因素 疾病 我们还将分析Tyro-3的细胞粘附特性 以及这种粘附影响其激酶活性的能力。 器单元 在发育过程中，粘附在神经元模式中起主要作用 并且可以影响成年CNS中突触连接的重塑。 我们将研究Tyro-3被磷酸化的观察结果， 向培养的海马神经元中添加谷氨酸。 通过 我们希望通过这些努力来了解Tyro-3的作用，Tyro-3是为数不多的 迄今为止描述的神经系统特异性酪氨酸激酶， 深入了解酪氨酸激酶一般在 信号转导事件对发育和 神经系统的功能。

During the development of the nervous system, a number of cellular processes which include cell proliferation, cell differentiation, cell adhesion, cell migration and cell death are required for the correct formation of neural structures and to obtain functional and reproducible connectivity between them. In the nervous system some of these cellular processes have been shown to be mediated or modulated by growth factors and their receptors. The receptors transduce responses upon activation its ligand through their tyrosine kinase domain the cytoplasmic tail. Examples of such growth factors/receptor pairs are NGF/trk, BDNK/trkB, and NT3/trkC. A yet uncharacterized receptor Tyro-3, belongs to this class and is the subject of our study. The overall goal of this project is to understand some of the functions, primarily in cell adhesion and to identify signal transduction pathways affected by the tyrosine kinas Tyro-3. This receptor has two immunoglobulin-like repeats and two fibronectin type-III repeats in its extracellular portion and intracellularly a functional tyrosine kinase domain, shown to be phosphorylated upon binding of its known ligand gas-6. We will determine the ultrastructural localization of Tyro-3 in the hoppocampus, in order to establish a possible role of Tyro-3 in synaptogenesis and synaptic plasticity. Preliminary data suggests that the Tyro-3 protein and mRNA are preferentially localizd in the dendritic layer of CA1 neurons. This structure has been demonstrated to be crucial for the establishment of short term memory and to be affected in Alzheimers disease. We will also analyze the cell adhesive properties of Tyro-3 and the ability of this adhesion to affect its kinase activity. Cel l adhesion plays a major role in neuronal patterning during development and can affect remodeling of synaptic connections in the adult CNS. We will study the observation that Tyro-3 is phosphorylated upon addition of glutamate to hippocampal neurons in culture. Through these efforts we hope to understand the role of Tyro-3, one of the few nervous ysstem specific tyrosine kinases described so far, and gain insight into the role played by tyrosine kinases in general in the signal transduction events important for the development and functioning of the nervous system.