Molecular tracking of quantum dot-linked aquaporins in living cell membranes

活细胞膜中量子点连接的水通道蛋白的分子追踪

基本信息

项目摘要

DESCRIPTION (provided by applicant): The broad goal of the proposed research is to understand the molecular arrangements of aquaporins in a living cell membrane. We wish to observe in real time the mechanisms by which aquaporins interact during water transport, and in conjuction with ion transport. The studies outlined here will directly address the molecular motions of aquaporins in the living membrane by tracking attached fluorescent particles called quantum dots. These studies will first focus on aquaporin arrangements alone. The physical motions and spatial arrangements of aquaporins during water transport will facilitate a better understanding of its role in response to brain injury and tumor cell migration. Co-localization experiments will determine in detail the interaction between aquaporins and potassium channels that may be crucial to the maintenance of ion gradients that preserve normal brain function and prevent epileptic seizures. The primary water channel in the brain is aquaporin-4. Since its discovery, its known role in the health of the central nervous system has been significantly expanded. When an injury occurs in the brain, swelling of soft tissues can cause severe damage due to their enclosure in the rigid cranium. Therefore, a path for rapid water transport must be readily available. Aquaporin-4 levels are upregulated in response to tumors, but this upregulation may actually serve to facilitate the spread of the aggressive types of cancer, which makes it an attractive target for cancer drug development. However, while the inhibition of aquaporin-4 may potentially slow the spreading of tumors, this may have severe consequences in other aspects of health. For example, the removal of aquaporin-4 leads to an increase the in the severity of edema caused by various types of brain injury. Recent evidence indicates a primary role of aquaporin-4 in the maintenance of potassium levels in the brain, possibly through molecular coupling of water and potassium channels. The removal of aquaporin-4 leads to a significant delay in the reuptake of potassium by cells in the neural cortex. Any imbalance in potassium levels in the brain can lead to the onset epileptic seizures. The range and severity of diseases that potentially involve aquaporin-4 is substantial. Epilepsy affects over 2 million Americans and results in a severly diminished quality of life. Malignant tumors in the brain are less common, but are almost universally fatal. An understanding of the molecular mechanishms behind these various roles of aquaporin-4 in the health of the central nervous system are a necessary step before considering the targeting of aquaporin-4 for treatment of disease.
描述(由申请人提供):拟议研究的主要目标是了解活细胞膜中水通道蛋白的分子排列。我们希望实时观察水通道蛋白在水转运过程中以及与离子转运结合时的相互作用机制。这里概述的研究将通过跟踪被称为量子点的附着的荧光粒子来直接解决活的细胞膜中水通道蛋白的分子运动。这些研究将首先集中在水通道蛋白的安排上。水通道蛋白在水运输过程中的物理运动和空间排列将有助于更好地了解其在应对脑损伤和肿瘤细胞迁移中的作用。共定位实验将详细确定水通道蛋白和钾通道之间的相互作用,这可能是维持维持正常大脑功能和防止癫痫发作的离子梯度的关键。大脑中主要的水通道是水通道蛋白-4。自从它被发现以来,它在中枢神经系统健康中的已知作用已经显著扩大。当大脑发生损伤时,软组织的肿胀会由于它们被坚硬的头盖骨包围而造成严重的损害。因此,必须有一条快速水上运输的道路。水通道蛋白-4水平因肿瘤而上调,但这种上调实际上可能有助于侵袭性癌症的扩散,这使其成为抗癌药物开发的一个有吸引力的靶点。然而,尽管抑制水通道蛋白-4可能会减缓肿瘤的扩散,但这可能会在健康的其他方面产生严重后果。例如,水通道蛋白-4的去除会增加各种类型的脑损伤引起的水肿的严重程度。最近的证据表明,水通道蛋白-4可能通过水和钾通道的分子耦合,在维持大脑中的钾水平方面发挥主要作用。水通道蛋白-4的去除导致神经皮质细胞对钾的重新吸收显著延迟。大脑中钾水平的任何失衡都可能导致癫痫发作。可能涉及水通道蛋白-4的疾病的范围和严重性是相当大的。癫痫影响了200多万美国人,导致生活质量严重下降。大脑中的恶性肿瘤不太常见,但几乎普遍是致命的。在考虑将水通道蛋白-4用于疾病治疗之前,了解水通道蛋白-4在中枢神经系统健康中的这些不同作用背后的分子机制是必要的步骤。

项目成果

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JONATHAN M CRANE其他文献

JONATHAN M CRANE的其他文献

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{{ truncateString('JONATHAN M CRANE', 18)}}的其他基金

Molecular tracking of quantum dot-linked aquaporins in living cell membranes
活细胞膜中量子点连接的水通道蛋白的分子追踪
  • 批准号:
    7389658
  • 财政年份:
    2007
  • 资助金额:
    $ 4.68万
  • 项目类别:

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