TARGETING OF THE SF HGF RECEPTOR TO THE BASOLATERAL DOMAIN OF POLARIZED EPITHELIAL-CELLS

Scatter Factor, also known as Hepatocyte Growth Factor (SF/HGF), has p leiotropic functions including direct control of cell-cell and cell-su bstrate adhesion in epithelia. The subcellular localization of the SF/ HGF receptor is controversial. In this work, the cell surface distribu tion of the SF/HGF receptor was studied in vivo in epithelial tissues and in vitro in polarized MDCK monolayers. A panel of monoclonal antib odies against the beta chain of the SF/HGF receptor stained the basola teral but not the apical surface of epithelia lining the lumen of huma n organs. Radiolabeled or fluorescent-tagged anti-receptor antibodies selectively bound the basolateral cell surface of MDCK cells, which fo rm a polarized monolayer sealed by intercellular junctions, when grown on polycarbonate filters in a two-chamber culture system. The recepto r was concentrated around the cell-cell contact zone, showing a distri bution pattern overlapping with that of the cell adhesion molecule E-c adherin. The basolateral localization of the SF/HGF receptor was confi rmed by immunoprecipitation after domain selective cell surface biotin ylation. When cells were fully polarized the SF/HGF receptor became re sistant to non-ionic detergents, indicating interaction with insoluble component(s). In pulse-chase labeling and surface biotinylation exper iments, the newly synthesized receptor was found exclusively at the ba solateral surface. We conclude that the SF/HGF receptor is selectively exposed at the basolateral plasma membrane domain of polarized epithe lial cells and is targeted after synthesis to that surface by direct d elivery from the trans-Golgi network.