ROLE OF BRAIN SPECIFIC PROTEINS IN NERVE FUNCTION

大脑特异性蛋白质在神经功能中的作用

• 批准号: 3403544
• 负责人: THOMAS C VANAMAN
• 金额: $ 20.27万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-04-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3403544
• 关键词: adenosine triphosphate; adenosinetriphosphatase; calcineurin; calcium; calcium channel; calcium flux; calmodulin; cell growth regulation; cell membrane; chemical binding; enzyme linked immunosorbent assay; enzyme mechanism; high performance liquid chromatography; hippocampus; human tissue; immunoglobulin G; isozymes; kindling; laboratory rabbit; laboratory rat; membrane transport proteins; molecular site; phosphorylation; protein kinase A; protein kinase C; protein structure function; synaptosomes; tissue /cell culture

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.

膜Ca 2+泵ATP酶家族是维持细胞膜钙离子浓度的关键。 静息状态的细胞质游离Ca 2 +-ATP酶水平， 内膜的结构、功能和调节 属性和生理作用。 如进度报告所述， 和重要性章节，在 动物细胞质膜Ca ~（2+）泵的研究 调控 该酶的九种不同亚型的结构具有 从它们各自的cDNA的研究中推断出来。 基于其 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。 虽然各地区 形成核心酶的分子似乎在很大程度上是保守的， 所有亚型，负责调节的分子的C-末端， 活性在不同的同种型之间有很大的不同。 这提供了以下 根据不同的活动，以满足需求的基础 不同的生理环境。 阐明监管性质 个体同种型的表达及其在 发展和响应细胞扰动是必不可少的， 全面了解动物体内钙离子依赖性调节 细胞 本申请的研究将主要集中在同种型 我们最初从牛和人的cDNA文库中克隆， 最密切相关的亚型，包括一个主要的亚型 人体红细胞 将采用各种方法研究 分子机制管理活动的调节， 钙调蛋白和可逆磷酸化，以确定相对 这些调节过程在体内的重要性，并检查 在多种条件下调节这种和其它同种型的表达， 生理条件。