Cell anchorage determines whether mammary tumor virus glycoproteins are processed for plasma membranes or secretion.
The subcellular localization of mouse mammary tumor virus (MMTV) glycoproteins was analyzed in infected and cloned rat hepatocarcinoma cells cultured with the MMTV transcriptional inducer dexamethasone. When reacted with protein A-coated erythrocytes in the presence of antisera specific for viral glycoproteins or with fluorescent antisera, only some of the cells acquired surface label. This diversity was dependent on cell anchorage to the substratum. In general, the more rounded, less adherent cells contained the MMTV glycoproteins on their surfaces, whereas the flatter, more adherent cells did not. After a change in adherence, a delay preceded complete remodeling of the plasma membranes. Fluorescent antibody studies of fixed cells and analyses of viral glycoprotein synthesis and shedding using L-[35S]methionine indicated that the different expression of MMTV glycoproteins in round versus flat cells is caused by a switch in posttranslational processing. In round cells, the MMTV-encoded precursor glycoprotein is proteolytically cleaved and then transported to plasma membranes as a complex of two subunits, the smaller being the membrane anchor. In flat adherent cells, the smaller subunit is rapidly degraded in an intracellular organelle and the larger is then secreted into the medium. As indicated by labeling of cells with 125I, the concentrations of several host-encoded plasma membrane components are also influenced by cell anchorage. We propose that this switch in cell surfaces and in secretions dependent upon cell-substratum attachments may be a common control mechanism important for embryogenesis, wound healing, and cancer.
D000818:Animals; D001692:Biological Transport; D002448:Cell Adhesion; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000378:metabolism*; D007467:Iodoproteins / Q000032:analysis; D008324:Mammary Tumor Virus, Mouse / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D011499:Protein Processing, Post-Translational; D051381:Rats; D014764:Viral Proteins / Q000378:metabolism*
D006023:Glycoproteins; D007467:Iodoproteins; D008565:Membrane Proteins; D014764:Viral Proteins; D003907:Dexamethasone