Molecular determinants of ion channel trafficking in neural cells

所有的运动和感觉都是由非常小的分子（如钠离子和钙离子）进出神经系统细胞所控制的。被称为“离子通道”的特殊蛋白质孔提供了通过神经细胞周围不可渗透的脂质膜的调节通道。因此，大脑的功能和学习依赖于这些离子通道蛋白精确地传递到细胞中的适当位置，以及它们在这些膜上的稳定性。由于离子通道是大而复杂的蛋白质，我们尚未完全了解这些过程背后的分子机制。这个研究项目利用了我的实验室在泛连接蛋白离子通道方面公认的专业知识，以及我们对锚蛋白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，我建议通过检查泛内联蛋白和锚蛋白B中的特定元素以及与其他蛋白质的物理相互作用，研究如何将泛内联蛋白和锚蛋白B传递到发育和成熟神经细胞的适当位置。这个研究项目将有助于我们了解神经细胞中调节离子通道传递和稳定性的分子因素的长期目标。此外，该项目将招收至少18名本科和研究生学术课程的高素质人才（HQP），从而为加拿大HQP的科学培养做出重要贡献。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，为他们未来在加拿大的学术研究和生物技术行业提供培训和就业机会。

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.