Molecular determinants of ion channel trafficking in neural cells

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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.