IBN-9604729 Brandt Calcium plays an integral role in regulating cellular function. It exerts its effects in the cell through interactions with a variety of specialized proteins. One of these proteins is the plasma membrane (PM) calcium pump. PM calcium pumps remove calcium from the cell, while consuming ATP to drive the reaction. It has recently been found that genetic manipulation to block production of one type of PM calcium pumps in a neuronal cell line prevented this cell from developing into a mature nerve cell when treated with nerve growth factor. This observation suggested that PM calcium pumps may be important in nerve cell development and regeneration. Further, it was found that a class of steroids known as glucocorticoids, which have been known to prevent the type of neurons used in these studies from developing into mature nerve cells, had a greatly enhanced effect when PM calcium pump production was blocked. From these two observations it was hypothesized that PM calcium pumps might be involved in controlling calcium levels in the cell responsible for determining how effective glucocorticoids are in preventing neuronal development. The studies to be undertaken as part of this research project will first examine changes in internal calcium levels that might be affecting the efficiency of glucocorticoid action by interacting with another calcium-regulated protein called calreticulin. If changes in internal calcium levels are found, then the underlying alteration in biochemical properties will be determined by studying possible changes in proteins that regulate calcium levels in the cell, among these proteins will be the PM calcium pumps. The ultimate goal of this research program will be to better understand the mechanisms of calcium regulation that affect nerve cell development and regeneration.
