INTESTINAL CELL MEMBRANES: STRUCTURE AND FUNCTION

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Current research on the cell surface membrane is based on the premise that the cell communicates with its microenvironment and adjacent cells, and that such communication affects a cell's behavior, determines the cell's role in tissue organization and allows control of cell function to be integrated with whole body needs. We have been studying these possible functions of cell surface membrane by examining intestinal epithelial cells. Our major efforts are in relating plasma membrane structure to the polarization of functions of the intestinal epithelial cell. The approach is based on examination of glycoprotein structure, synthesis and turnover in membranes, and the relationship to a specific intestinal function, vitamin D-dependent Ca++ transport. Methods have been established to obtain rat intestinal epithelial cells as isolated cells representing a crypt-to-villus gradient of differentiation, and techniques have been described for purification of Golgi, lateral-basal and microvillus membranes. More recently, we have developed a method for purifying intestinal epithelial cell nuclei. The specific aims of our research are 1) to isolated and characterize the 1,25(OH)2 vitamin D3 dependent Golgi glycoproteins responsible for 1,25(OH)2D3 dependent Ca++ uptake by Golgi membranes, 2) to characterize the intracellular pathways of intestinal cell membrane glycoprotein synthesis using 1,25(OH)2D3-dependent membrane glycoproteins as indicators, 3) to further characterize the molecular mechanisms of 1,25(OH)2D3 action on intestinal nuclei and intestinal glycoprotein synthesis, and 4) to describe the differences in membrane glycoproteins and their synthesis that are associated with cell turnover, differentiation and among the different parts of the intestine. These studies will use the intestine as a model tissue with which to define the biochemical and molecular mechanisms by which the cell membrane controls and contributes to the organization of a cell within the restrictions and metabolic requirements of its tissue structure and function. These studies should also define the role of the plasma membrane in the pathogenesis and pathophysiology of nutritional and intestinal diseases.