Studies on the local control by nerve growth factor of the outgrowth of neurites in PC12D cells.

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The outgrowth of neurites was induced in PC12D cells that were treated not only with NGF but also with bFGF,abcAMP,or staurosporine. Simultaneous activation and nuclear translocation of MAP kinases were observed in cells treated with NGF or bFGF.But staurosporine and abcAMP induced no or slight activation of MAPK.Because of the similarity between PC12D cells and primed cells, the activation and nuclear translocation of MAPK might be required for transcriptiondependent differentiation step but might not be necessary for the elongation of neurites. The outgrowth of neurites from PC12D cells was not blocked by the addition of a protein-synthesis inhibitor, cycloheximide in which protein synthesis was reduced by 97%. We have examined to demonstrate local contral by NGF of the outgrowth of neuries from PC12D cells. (1) The neurite outgrowth and their survival can be induced by NGF in enucleated PC12D cells. (2) Individual giant neurites of a single cell (fused PC12D cells) can respond independently to the NGF.(3) The dissected giant neurites are maintained longer in medium containing NGF than not. (4) The rapid formation of ruffles in response to NGF which appears to be based on increased cell-substratum adhesion, lead to the subsequent formation of neurites. The observation indicates that the NGF-dependent maintenance or extension of neurites might be controlled within the neurites themselves. Any NGF-promoted changes that promote a local increase in cellsubstratum adhesion could be responsible for elongation and initiation of neurites.