Biology of p5-type cation-transporting atpases

我的研究项目的目标是了解膜蛋白维持正常神经细胞功能所必需的钙水平的正确平衡的机制。细胞膜含有各种已被充分描述的转运蛋白，它们使钙能够进入（或离开）细胞。我最近分离出了五个新的人类P5型转运蛋白亚家族成员，称为ATP 13A1至ATP 13A5，归类为钙转运蛋白。这是特别感兴趣的，因为钙在神经元生理学中起着核心作用，包括神经元成熟、分化和细胞死亡。目前提出的研究计划的主要目标是了解P5型泵的生物学功能，提供实验证据表明它们参与钙稳态，并表明它们具有与主要已知钙转运蛋白不同的功能。重点将放在它们在发育和成熟的神经系统中的生物学作用上。我的实验室整合了遗传学，神经科学和细胞生理学领域的各种现代分子方法来研究蛋白质的生化特性。我将研究正常大脑发育过程中的表达和调节机制，以及与其活动缺陷相关的潜在生理变化。这项研究计划将为膜离子易位的性质提供新的见解，并将有助于阐明钙调节的新的和独特的机制。

The goal of my research program is to understand the mechanisms by which membrane proteins maintain the right balance of calcium level essential for normal neuronal cell function. Cell membranes contain various well described transport proteins, which enable calcium to enter (or leave) the cell. I have recently isolated five novel members of the human subfamily of P5-type transporters, called ATP13A1 to ATP13A5, classified as calcium transporters. This is of special interest, since calcium plays a central role in neuronal physiology including neuronal maturation, differentiation, and cell death. The main objectives of the currently proposed research program are to understand the biological function of P5-type pumps, to provide experimental evidence that they are involved in calcium homeostasis, and to show that they have distinct functions from the major known calcium transporters. The emphasis will be on their biological role in the developing and mature nervous system. My lab integrates various modern molecular methodologies in the area of genetics, neuroscience and cell physiology to study biochemical properties of proteins. I will study the expression and mechanisms of regulation during normal brain development, and potential physiological changes associated with defects in their activity. This program of study will provide new insights into the nature of membrane ion translocation, and it will help to elucidate novel and distinctive mechanisms of calcium regulation.