Balance of two secretion pathways of nerve growth factor in PC12 cells changes during the progression of their differentiation, with a decrease in constitutive secretion in more differentiated cells

Proteins are secreted from animal cells by either a constitutive or a regul ated pathway. When cDNA of nerve growth factor (NGF) was introduced into PC 12 cells, these cells produced and secreted active NGF, where NGF was secre ted not only in constitutive but also in activity-dependent regulated way a ccording to the results of pulse-chase and ELISA studies, The regulated sec retion was caused by depolarization, cyclic AMP analogue, or beta-adrenergi c agonist but not by glutamate or carbachol. Because these transfected cell s differentiated into a morphology indistinguishable from that incubated wi th NGF protein, we next compared the secretion pathways of NGF from PC12 ce lls at different stages of the differentiation. NGF was secreted in both co nstitutive and regulated way at 2 and 7 days after the transfection of NGF- cDNA, but the constitutive secretion of NGF from the more differentiated ce lls of Day 7 was decreased and mature NGF tended to accumulate in the cells . These results indicate that the neurotrophin secretion mechanism is intim ately regulated in the course of the differentiation of PC12 cells, Such a change in the protein secretion pathway might have an profound role in the development of neurons. J. Neurosci. Res. 59:632-642, 2000, (C) 2000 Wiley- Liss, Inc.