Epithelial cells, which comprise 50% of all cells in the body [and account for 90% of all human cancers] have as a defining function the creation and maintenance of physiological compartments of the body. Epithelial cells not only physically separate different environments; they regulate selective exchange between them. This requires that the cells' opposing surfaces be functionally differentiated; hence, epithelial cells are functionally polarized. This polarization is accomplished through cooperative formation and dynamic maintenance of junctional complexes between adjacent cells and by the selective or differential delivery and retention of membrane proteins and lipids to one pole or the other each cell. The projects in this program study selective delivery of components to apical and basolateral membrane domains. A variety of perspectives are taken and different techniques are used, but at the same time there is a common focus in all four projects on the Golgi complex, considering its lateral organization and heterogeneity, traffic, composition, and integrity and maintenance of its spatial orientation. Edidin (Project 1) focuses on the lateral organization of Golgi membrane and plasma membrane proteins, particularly GPI-proteins, and lipids, required for the polarized traffic of these molecules. Hubbard (Project 3) focuses on intracellular routes and mechanisms for the polarized delivery and retention of membrane proteins, with emphasis on the endosomal/transcytotic system. Machamer (Project 4) focuses on the mechanisms of the organization and composition of the Golgi complex that important for sorting lipids and proteins destined for the plasma membrane, while maintaining its own integrity. Schroer (Project 6) focuses on the cytoskeletal machinery that maintains the polarized intracellular architecture of epithelial cells and on the routes traveled by vesicles between cytoplasmic membranes and between cytoplasm and surface.
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