ROLE OF BRAIN SPECIFIC PROTEINS IN NERVE FUNCTION

膜钙泵ATPase家族对维持 细胞内游离钙-三磷酸腺苷酶的静息水平不同于 内膜在结构、功能和调节方面的差异 以及在生理上的作用。如进度报告所述 和重要部分，在以下方面取得了实质性进展 动物细胞质膜钙泵及其功能的研究 监管。该酶的九种不同亚型的结构有 是从对它们各自的cDNA的研究中推断出来的。基于他们的 一级结构，这些异构体是差异剪接的产物 至少四个不同基因的初级转录本。而这些地区 形成核心酶的分子似乎在很大程度上是保守的 所有的异构体，负责调节的分子的C末端 不同的异构体之间活性有很大差异。这提供了 对活动进行差别化监管的基础，以满足 不同的生理环境。对调节特性的说明 的个体亚型及其表达的调节 发展和对细胞扰动的反应是必不可少的 全面了解动物体内钙离子依赖的调节 细胞。在这个应用中的研究将主要集中在异构体上 我们最初从牛和人的cDNA文库中克隆了这个基因 与它关系最密切的亚型，包括主要的亚型之一 人类的红细胞。将使用多种方法来研究 调控活性的分子机制通过 钙调蛋白与可逆性磷酸化，以确定相对 这些调节过程在体内的重要性，并检查 该异构体和其他异构体在不同种类的 生理条件。

The family of membrane Ca2+-pumping ATPases are essential for maintaining resting state levels of cytosolic free Ca2+-ATPases which are distinct from those of internal membranes in structure, function, and regulatory properties and in physiological roles. As set forth in the PROGRESS REPORT and SIGNIFICANCE sections, substantial progress has been made in the studies of the plasma membrane Ca2+ pump in animal cells and it's regulation. The structures of nine distinct isoforms of the enzyme have been deduced from studies of their respective cDNAs. Based on their primary structures, these isoforms are products of differential splicing of primary transcripts of at least four distinct genes. While the regions of the molecule which form the core enzyme appear to be largely conserved in all isoforms, the C-terminus of the molecule responsible for regulation of activity differs substantially among different isoforms. This provides the basis for differential regulation of activity to meet the needs of different physiological settings. Elucidation of the regulatory properties of individual isoforms and the regulation of their expression during development and in response to cellular perturbation is essential for gaining a complete understanding of Ca2+-dependent regulation in animal cells. Studies in this application will focus primarily on the isoform which we initially cloned from bovine and human cDNA libraries and the isoforms most closely related to it, including one of the major isoforms of the human erythrocyte. A variety of approaches will be used to study the molecular mechanisms governing the regulation of activity through calmodulin and reversible phosphorylation, to determine the relative importance of these regulatory processes in vivo, and to examine the regulation of expression of this and other isoforms under a variety of physiological conditions.