Epithelial cells regulate the exchange of macromolecules between the external environment and underlying tissues. This selective exchange is made possible by the impermeability of the monolayer to both large and small molecules and by specialized endocytic pathways that allow transit of macromolecules across these cells. Epithelia characteristically have discrete plasma membrane domains at the apical and basolateral poles of the cell that are separated by tight junctions. Each domain has a distinct protein and lipid composition which is maintained despite an enormous flux of membrane traffic to and from each surface. In Madin-Darby canine kidney (MDCK) cells, for instance, an area of plasma membrane equivalent to 40% of the cell surface is endocytosed per hour.

It has been known for some time that epithelial cells, both in vitro and in vivo, are capable of endocytosing macromolecules from both their apical and basolateral cell surfaces. The fate of these internalized macromolecules depends on the marker being analyzed and the cell type being studied. An excellent model system to analyze membrane traffic in polarized epithelial cells is the polymeric immunoglobulin receptor (pIgR). Upon delivery to the basolateral cell surface, the pIgR binds its ligand (IgA), and receptor-ligand complexes are endocytosed and delivered to the basolateral early endosomes (BEE). The pIgR-ligand complexes are then directly translocated, in a microtubule dependent process (i.e. this step is nocodazole sensitive), from the BEE to the apical recycling endosome (ARE). Subsequently, the pIgR-ligand complex exits the ARE and at or en route to the apical surface, the ligand binding domain of the receptor is proteolytically cleaved, releasing it and its bound ligand into the apical medium. This released ligand binding domain of the receptor is termed secretory component (SC).

Current projects in the laboratory include:

I. Analysis of endocytic pathways in polarized MDCK cells
II. Regulation of endocytic traffic by Rho family GTPases
III. Stretch-regulated endocytosis/exocytosis in bladder uroepithelium