Scanning and transmission electron microscope studies were carried out on the rapid cell surface responses of cultured newborn rat sympathetic neurons to nerve growth factor (NGF), a substance that promotes their survival and differentiation. The somas of sympathetic neurons continuously exposed to NGF or deprived of the factor for 4-5 h have a very smooth surface. After readdition of NGF to the latter type of cultures, there is rapidly initiated a transient, sequential change in the cell surface. Microvilli and small ruffles appear within 30 s and are most prominent by 1 min. By 3 min of exposure, the microvilli and ruffles decrease in prominence, and by 7 min the somal surface is again smooth. By 30 s after NGF readdition, as increase in the number of 60- tp 130-nm coated pits is also detectable. This increase reaches a maximum of about threefold from 0.5 to 3 min and then gradually decreases. Alterations in the surface did not occur on the nonneuronal cell types present in the cultures and were not observed in response to another basic protein (cytochrome c) or to physical manipulation. Changes in cell surface architecture induced by NGF in normal sympathetic neurons and, as previously described, in PC12 pheochromocytoma cells indicate that such responses may present or reflect primary events in the mechanism of the factor's action.

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