Sarco(endo)plasmic Reticulum Calcium ATPse 3

描述（由申请人提供） 血管形态和功能的调节是一个动态过程， 血管细胞的反应和活动的复杂整合， 各种刺激。 为了响应这些刺激，血管系统可以 介导许多生理过程，迅速改变血管直径， 控制血液流动，生长新的血管成分（血管生成）。 虽然 这些看似独立的活动，所有这些行动都构成了 其中血管系统维持组织内稳态并因此代表了 单一但高度集成的功能。 我的研究生涯目标是 建立跨学科血管研究计划， 了解血管形态和功能相关的分子决定因素 支持组织稳态。 研究发展计划，以达到 这一目标的核心是整合重点研究项目， 检测内皮细胞信号转导的特异性， 血管重建过程中血管张力的建立，以及遗传因素 控制血管生长。 该计划的目标是建立一个 高度互动的研究团队，扩大合作， 成像科学家，并获得分子遗传学的进一步专业知识。 在大血管内皮细胞中，细胞内钙池由 两种肌细胞（内皮细胞）胞浆钙ATP酶（SERCA）; 表达的SERCA 3和普遍存在的SERCA 2b泵。 研究的目标 这将检查内皮细胞的信号转导，并提供基础， 是为了验证一个假设， 内皮细胞利用不同的细胞内钙池，定义如下 这两个SERCA泵，介导对不同类型刺激的反应， 通过完成四个具体目标，证明钙池 SERCA 3参与内皮细胞和血管内皮细胞的亚群， 生理反应。 具体目标1和2将描述 SERCA 3和SERCA 2b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 通过检查SERCA 3在血管功能中的作用来检测完整动物。 小鼠 缺乏SERCA 3泵的小鼠和来自这些小鼠的内皮细胞 为这些研究提供了实验基础。 选择性差异 在两只小鼠的细胞和血管之间观察到的差异可以归因于 缺乏由SERCA 3建立的钙储存，并表明这些过程 依靠这个钙池。 这些目标的实现将进一步 深入了解如何特异性，从而调节信号转导， 内皮细胞建立。 (End摘要）

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)