Sarco(endo)plasmic Reticulum Calcium ATPse 3

肌（内）质网钙 ATPse 3

• 批准号: 6319117
• 负责人: JAMES B HOYING
• 金额: $ 7.64万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-13 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6319117
• 关键词: angiogenesis; biological signal transduction; calcium flux; calcium transporting ATPase; endoplasmic reticulum; laboratory mouse; protein localization; protein structure function; sarcoplasmic reticulum; vascular endothelium

DESCRIPTION (provided by applicant) Regulation of vascular form and function is a dynamic process that depends on the complex integration of responses and activities by vascular cells to a variety of stimuli. In response to these stimuli, the vascular system can mediate numerous physiological processes, rapidly alter vessel diameter to control blood flow, and grow new vessel elements (angiogenesis). Although seemingly separate activities, all of these operations constitute the means by which the vascular system maintains tissue homeostasis and thus represent a single, albeit highly integrative, function. My research career goal is to establish an interdisciplinary vascular research program aimed at understanding the molecular determinants of vascular form and function related to supporting tissue homeostasis. The research development plan to attain this goal is centered around the integration of focused research projects examining specificity in endothelial cell signal transduction, the establishment of vascular tone during vessel remodeling, and the genetic control of vascular growth. The objectives of this plan are to create a highly interactive research team, expand collaborations with accomplished imaging scientists, and gain further expertise in molecular genetics. In large vessel endothelial cells, intracellular calcium pools are managed by two sarco(endothelial cell)plasmic calcium ATPases (SERCA); the uniquely expressed SERCA3 and the ubiquitous SERCA2b pumps. The goal of the research that will examine endothelial cell signal transduction and provide the basis for expanding my collaborative efforts is to test the hypothesis that endothelial cells utilize distinct intracellular calcium pools, as defined by these two SERCA pumps, to mediate responses to different types of stimuli by demonstrating, through completion of four specific aims, that the calcium pool maintained by SERCA3 participates in a subset of endothelial cell and vascular physiological responses. Specific Aims I and 2 will characterize the functional specificity of the SERCA3- and SERCA2b-managed calcium pools within the endothelial cell. Specific Aims 3 and 4 will extend this analysis into the intact animal by examining the role of SERCA3 in vascular function. Mice deficient in the SERCA3 pump and endothelial cells from these mice will provide the experimental basis for these studies. Selective differences observed between cells and vessels of the two mice can be attributed to the absence of calcium stores established by SERCA3 and indicate those processes relying on this calcium pool. Completion of these aims will provide further insight into how specificity, and thus regulation, in signal transduction in endothelial cells is ,established. (End of Abstract)

描述(由申请人提供) 血管形态和功能的调节是一个动态的过程，依赖于 血管细胞对细胞的反应和活动的复杂整合 各种刺激。作为对这些刺激的反应，血管系统可以 调节众多生理过程，迅速改变血管直径以 控制血液流动，生长新的血管成分(血管生成)。虽然 看似独立的活动，所有这些行动都构成了通过 血管系统维持组织的动态平衡，因此代表着 虽然高度一体化，但功能单一。我的研究生涯目标是 建立跨学科的血管研究计划，旨在 了解与血管形态和功能相关的分子决定因素 来维持组织的动态平衡。要达到的研究发展计划 这一目标围绕着重点研究项目的整合展开。 检测内皮细胞信号转导的特异性， 血管重塑过程中血管张力的建立及其遗传学 控制血管生长。该计划的目标是创建一个 高度互动的研究团队，扩大与已完成的合作 成像科学家，并在分子遗传学方面获得进一步的专业知识。 在大血管内皮细胞中，细胞内钙池由 两种肌浆内皮细胞钙ATPase(SERCA)； 表达SERCA3和无处不在的SERCA2b泵。这项研究的目的 这将为研究内皮细胞的信号转导提供基础 扩大我的合作努力是为了检验这样一个假设 内皮细胞利用不同的细胞内钙池，如 这两个SERCA泵，通过以下方式调节对不同类型刺激的反应 通过完成四个具体目标，证明了钙池 由SERCA3维持，参与内皮细胞和血管的一个子集 生理反应。具体目标I和2将描述 SERCA3和SERCA2b管理的钙池的功能特异性 内皮细胞。具体目标3和4将把这一分析扩展到 通过检测SERCA3在血管功能中的作用完整的动物。老鼠 缺乏SERCA3泵和来自这些小鼠的内皮细胞将 为这些研究提供了实验依据。选择性差异 在两只小鼠的细胞和血管之间观察到的可以归因于 没有SERCA3建立的钙库，并表明这些过程 依靠这个钙池。完成这些目标将提供进一步的 洞察信号转导中的特异性，从而调节 血管内皮细胞已经建立。(摘要结束)