BIOLOGICAL ROLE OF PROTOCADHERINS IN CNS

中枢神经系统需要复杂的细胞间相互作用 它的结构形成和无数的功能，以及细胞粘附 似乎在这些事件中扮演着重要角色。 理解细胞 粘附分子介导钙离子依赖的选择性细胞间粘附 在许多生物过程中。 然而，只有一种钙粘蛋白形式 中枢神经系统已经被广泛研究。 使用 聚合酶链反应，我们最近已经分离出许多cDNA， 对应于新的钙粘蛋白和钙粘蛋白相关蛋白，称为 原钙粘蛋白，来自大鼠和人脑cDNA制备物。 在这 建议的研究，我们将集中在原钙粘蛋白，因为许多这些 蛋白质主要在大脑中表达，因为它们的表达是 因为它们具有以下特性： 粘附蛋白 拟议研究的长期目标是 阐明原钙粘蛋白在中枢神经系统中的生物学作用 神经系统 我们将研究这些新的基本性质 分离的原钙粘蛋白，以阐明其作用，特别是 在神经组织形成和维持中的作用。 我们将（1）确定 两种原钙粘蛋白的全部氨基酸序列;（2）表达 原钙粘蛋白在各种细胞中形成克隆的cDNA，并检查它们的基本 生化和生物学特性;（3）检查组织和细胞 这些原钙粘蛋白的定位，以及它们的调节， 表达;（4）检测原钙粘蛋白异位表达对细胞凋亡的影响 pc 2及其变异形式在神经视网膜发育中的作用 对原钙粘蛋白pc 2基因的结构进行了分析。 结果将提供 基本信息对理解有价值的信息 这些蛋白质在生理和 病理条件，并可能黑尔影响了解一些 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.