Selective loss of pertussis toxin-sensitive G-proteins from the plasma membrane after antibody-induced internalization of T-cell surface molecules.
Antibody-induced antigenic modulation occurs after binding of antibodies to a variety of cell surface proteins. It is characterized by aggregation and subsequent loss of the molecules from the cell surface, usually by internalization. In this study we have investigated the effect of modulation of the T-cell antigen receptor complex (TCR) and the transferrin receptor (TFR) on the distribution of cholera toxin (CTx)- and pertussis toxin (PTx)-sensitive GTP binding proteins in human T-lymphocytes. Modulation of both the TCR and the TFR induced a selective shift of PTx-sensitive G-proteins from the plasma membrane to a high density membrane fraction enriched for lysosomal membranes. The distribution of CTx-sensitive G-proteins was unaffected. This shift was found in both the T-cell leukemia line Jurkat and in normal T-cells. The loss of PTx-sensitive G-proteins from the plasma membrane required approximately 15 h to be complete and was not inhibited by cycloheximide. It had no influence on T-cell triggering via anti-T-cell receptor antibodies and is unrelated to the inactivating effect of TCR-modulation on T-cell signalling. The loss of PTx-sensitive G-proteins was not accompanied by greater sensitivity to stimuli raising cAMP concentration. These results show that PTx-sensitive G-proteins can be selectively depleted from the plasma membrane by antibody treatment of T-cells.
Gerardy-Schahn
R
R
1. Department of Medicine, University of Mainz, Federal Republic of Germany.
Mittrücker
H W
HW
Schultze
U
U
Fleischer
B
B
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism; D002458:Cell Fractionation; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000502:physiology; D002499:Centrifugation, Density Gradient; D003600:Cytosol / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D009243:NAD / Q000378:metabolism; D037342:Pertussis Toxin; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D010566:Virulence Factors, Bordetella; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium