Intracellular receptor binding and nuclear transport of nerve growth factor in intact cells and a cell-free system

Nuclear uptake of 125I-labeled nerve growth factor (NGF) by cells that either express or do not express the cell surface receptor was tested using intact cells and a cell-free system. Intracellular and consequently nuclear uptake of NGF in intact cells was dependent on the presence of surface NGF receptor, whereas nuclear uptake in a cell-free system did not correlate with cell surface receptor expression. In the cell-free system, nuclear transport was inhibited when NGF receptor was being actively synthesized. Preincubation of intact cells with unlabeled NGF, cycloheximide, puromycin, or actinomycin D increased nuclear uptake up to threefold. The data suggest that, in intact cells, NGF transported into the cell via the surface receptors is also bound by the NGF receptor being synthesized in the cytoplasm. NGF taken up by the nucleus inhibited transcription of ribosomal RNA genes by 70% and, in turn, inhibited cell proliferation by 60%. A direct effect of NGF on transcription is discussed.