TY - JOUR
T1 - Cell anchorage determines whether mammary tumor virus glycoproteins are processed for plasma membranes or secretion
AU - Kabat, David
AU - Gliniak, Brian
AU - Rohrschneider, Larry
AU - Polonoff, Ethel
PY - 1985/12/1
Y1 - 1985/12/1
N2 - 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 MMTVencoded 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 1251, 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 secetions dependent upon cell-substratum attachments may be a common control mechanism important for embryogenesis, wound healing, and cancer.
AB - 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 MMTVencoded 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 1251, 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 secetions dependent upon cell-substratum attachments may be a common control mechanism important for embryogenesis, wound healing, and cancer.
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U2 - 10.1083/jcb.101.6.2274
DO - 10.1083/jcb.101.6.2274
M3 - Article
C2 - 2999161
AN - SCOPUS:0022348141
SN - 0021-9525
VL - 101
SP - 2274
EP - 2283
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 6
ER -