Molecular determinants of ion channel trafficking in neural cells

神经细胞离子通道运输的分子决定因素

• 批准号: RGPIN-2017-03889
• 负责人: Swayne, LeighAnne
• 金额: $ 2.48万
• 依托单位: University of Victoria
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=666295
• 关键词: Molecular; determinants; ion; channel; trafficking

All movement and sensation are controlled by the passage of very small molecules, like sodium and calcium ions, in and out of the cells of the nervous system. Specialized protein pores, called “ion channels”, provide regulated access through the impermeable lipid membranes that surround nerve cells. Accordingly, brain functioning and learning depend on the precise delivery of these ion channel proteins to the appropriate location in the cell as well as their stability at these membranes. Because ion channels are large, complex proteins, we do not yet fully understand the molecular mechanisms underlying these processes. This research program capitalizes on my lab's recognized expertise in pannexin ion channels as well as new insights we have made into the cell biology of the ankyrin B ion channel anchoring (scaffold) protein. Building on this strong foundation, I propose to investigate how pannexins and ankyrin B are delivered to the appropriate places in developing and mature nerve cells, by examining specific elements within these proteins as well as physical interactions with other proteins. This research program will contribute to our long-term goal of understanding the molecular factors regulating the delivery and stability of ion channels in neural cells. Additionally, this program will involve at least 18 high-quality personnel (HQP) in undergraduate and graduate academic programs, thus making an important contribution to the scientific training of HQP in Canada. These HQP will develop technical and theoretical expertise in a range of cell biological analysis tools that will afford them future training and employment opportunities in academic research and the biotech industry in Canada.

所有的运动和感觉都是由非常小的分子，如钠和钙离子，进出神经系统细胞的通道控制的。特殊的蛋白质孔，称为“离子通道”，提供了通过神经细胞周围不渗透的类脂膜的调节通道。因此，大脑的功能和学习依赖于这些离子通道蛋白的准确输送到细胞中适当的位置，以及它们在这些膜上的稳定性。由于离子通道是大的、复杂的蛋白质，我们还没有完全了解这些过程背后的分子机制。这项研究计划利用了我的实验室在PAnnexin离子通道方面公认的专业知识，以及我们对Ankyrin B离子通道锚定(支架)蛋白的细胞生物学的新见解。在这个坚实的基础上，我建议通过检测这些蛋白质中的特定元素以及与其他蛋白质的物理相互作用，来研究联结蛋白和锚蛋白B是如何被运送到发育和成熟的神经细胞的适当位置的。这项研究计划将有助于我们的长期目标，即了解调节神经细胞离子通道输送和稳定性的分子因素。此外，该项目将包括至少18名本科和研究生学术项目的高素质人才(HQP)，从而为加拿大HQP的科学培训做出重要贡献。这些HQP将开发一系列细胞生物学分析工具的技术和理论专业知识，为他们提供未来在加拿大学术研究和生物技术行业的培训和就业机会。