BLOCKADE OF PLASMA-MEMBRANE CALCIUM-PUMPING ATPASE ISOFORM-I IMPAIRS NERVE GROWTH FACTOR-INDUCED NEURITE EXTENSION IN PHEOCHROMOCYTOMA CELLS

Numerous lines of evidence indicate that calcium signaling is essentia l for nerve growth factor (NGF)-directed neuronal cell differentiation . We report here that blocking production of the plasma membrane Ca2+- ATPase isoform 1 (PMCA1) in PC6 cells with antisense RNA impairs their ability to extend normal neurites in response to NGF. This result doe s not appear to be due to loss in NGF signaling as NGF-dependent tyros ine phosphorylation of erk1 and erk2, as well as expression of the NGF -inducible immediate early gene, NGFI-A, was observed in these cells. Resting cytosolic calcium levels did not appear to be altered in the a ntisense transfectants and release of calcium from internal bradykinin -sensitive calcium pools was unchanged. However, the rate of removal o f free cytosolic calcium following this release was reduced in the ant isense-transfected cells compared with controls. It is concluded that PMCA1 is involved in neurite extension and/or stabilization either thr ough moderation of local calcium levels, or by some other mechanism.