BIOLOGICAL ROLE OF PROTOCADHERINS IN CNS

中枢神经系统需要复杂的细胞间相互作用。 因为它的结构形成和无数的功能，以及细胞黏附 似乎在许多这样的事件中扮演着重要的角色。了解单元格 黏附分子，介导钙离子依赖的选择性细胞间黏附 在许多生物过程中。然而，只有一种类型的钙粘素形式 人们对中枢神经系统进行了广泛的研究。vbl.使用 聚合酶链式反应，我们最近分离出了许多cDNA 与新的钙粘附素和钙粘附素相关蛋白相对应，称为 原钙粘附素，来自大鼠和人脑的cdna制剂。在这 我们将重点研究原钙粘附素，因为其中许多 蛋白质主要在大脑中表达，因为它们的表达是 在发育上受调控，因为它们具有 黏附蛋白。拟议研究的长期目标是 原钙粘附素在中枢神经系统中的生物学作用 神经系统。我们将研究这些新结构的基本性质 分离的原钙粘附素，以阐明它们的作用，特别是 在神经组织的形成和维持中的作用。我们将(1)确定 两个原钙粘附素的全部氨基酸序列；(2)表达 原钙粘附素在不同的细胞中形成克隆的cDNA，并检查它们的基础 生化和生物学特性；(3)检查组织和细胞 这些原钙粘附素的定位及其调控 (4)检测异位表达原钙粘附素的效果。 PC-2及其改变形式对神经视网膜发育的影响； 鉴定原钙粘附素PC2基因。结果将提供 基本信息对了解有价值的信息有价值 这些蛋白质在生理和心理状态下的生物学作用 病理条件，并可能对理解一些 神经疾病，如发育障碍和神经变性。

The central nervous system requires complicated cell-cell interactions for its structural formation and myriad functions, and cell adhesion seems to play an important role many of these events. Understanding cell adhesion molecules, mediate Ca2+ dependent, selective cell-cell adhesion in many biological processes. However, only one type of cadherin form the central nervous system has been studied extensively. Using polymerase chain reaction, we have recently isolated many cDNAs that correspond to new cadherins and to cadherin-related proteins, termed protocadherins, from rat and human brain cDNA preparations. In this proposed study we will focus on protocadherins, because many of these proteins are expressed mainly in brain, because their expression is regulated developmentally, and because they have the properties of adhesion proteins. The long-term goal of the proposed study is elucidation of the biological role of protocadherins in the central nervous system. We will study the basic properties of these newly isolated protocadherins in order to clarify their role, especially the role in nervous tissue formation and maintenance. We will (1) determine the entire amino acid sequences of two protocadherins; (2) express the protocadherins form cloned cDNAs in various cells and examine their basic biochemical an biological properties; (3) examine the tissue and cellular localization of these protocadherins, and the regulation of their expression; (4) examine the effect of ectopic expression of protocadherin pc 2 and its altered form on development of neural retina; and (5) characterize the gene of protocadherin pc2. The results will provide basic information i valuable for information valuable for understanding the biological role of theses proteins under physiological and pathological conditions, and may hale implications for understanding some neural disease, such as developmental disorders an neural degeneration.