Biology of P5-type cation-transporting ATPases

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During the development of the central nervous system, neuronal activity drives the specification and maturation of synaptic connections. The process of neuronal maturation and formation of functional contacts is tightly controlled by calcium-dependent gene expression. Calcium plays a central role in neuronal function including maturation, differentiation, and death. I have recently isolated five novel proteins, called ATP13A1 to ATP13A5, classified as calcium transporters. They are members of the P5-type subfamily of membrane ion transporters. The main focus of the accompanying Discovery research program is to understand the biological role of these transporters in the developing and mature nervous system. My main objective is to provide experimental evidence that the human P5 transporters are involved in calcium homeostasis and that they have distinct functions from the major known calcium pumps. To achieve the goals set in my research program I will require a computer-controlled Mastercycler real-time PCR system for quantified measurement of gene expression in the developing brain. My laboratory will be the first to study molecular mechanisms of the human subfamily of P5-type transporters. The real-time PCR system will be used right away for initiating the experiments described in my accompanying Discovery application. My currently proposed research will provide new insights into the nature of membrane ion translocation, and it will help to elucidate novel and distinctive mechanisms of calcium regulation in the nervous system.