Conversion of nerve growth factor-receptor complexes to a slowly dissociating, Triton X-100 insoluble state by anti nerve growth factor antibodies.
Two populations of nerve growth factor (NGF) receptors can be distinguished on PC12 cells and have been termed "fast" and "slow" receptors on the basis of their respective rates of dissociation. Since a slowly dissociating state of the NGF receptor could be produced by receptor clustering, we sought to examine the effects of artificially clustering NGF-receptor complexes by using anti-NGF antibodies. At an 125I-NGF concentration of 500 pM, slow receptors account for 25% of the total NGF binding. However, if 125I-NGF is first bound to the cell surface and an anti-NGF immunoglobulin G (IgG) is added subsequently, greater than 90% of the total binding becomes slowly dissociating. Anti-NGF IgG also changes the proportion of Triton X-100 insoluble NGF binding from 10% to 50%, possibly reflecting an association of the NGF receptor with the cytoskeleton. The effects on NGF binding of low concentrations of anti-NGF IgG could be enhanced by the addition of goat anti-rabbit IgG. Neither Fab fragments nor an anti-NGF monoclonal antibody affects NGF binding, indicating that the cross-linking capacity of anti-NGF IgG is required for its activity. Wheat germ agglutinin (WGA), a multivalent lectin, also converts NGF binding into a predominantly slowly dissociating, Triton X-100 insoluble state. Both WGA and anti-NGF IgG produce their effects on NGF binding at 37 and 4 degrees C and protect the 125I-NGF-receptor complex from protease digestion.(ABSTRACT TRUNCATED AT 250 WORDS)
D000310:Adrenal Gland Neoplasms; D000818:Animals; D000906:Antibodies; D000936:Antigen-Antibody Complex / Q000032:analysis*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003902:Detergents; D007700:Kinetics; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism*; D017830:Octoxynol; D010673:Pheochromocytoma; D011092:Polyethylene Glycols; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor; D012995:Solubility
D000906:Antibodies; D000936:Antigen-Antibody Complex; D003902:Detergents; D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D011092:Polyethylene Glycols; D017830:Octoxynol