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 essential for nerve growth factor (NGF)-directed neuronal cell differentiation. We report here that blocking production of the plasma membrane Ca(2+)-ATPase isoform 1 (PMCA1) in PC6 cells with antisense RNA impairs their ability to extend normal neurites in response to NGF. This result does not appear to be due to loss in NGF signaling as NGF-dependent tyrosine 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 antisense transfectants and release of calcium from internal bradykinin-sensitive calcium pools was unchanged. However, the rate of removal of free cytosolic calcium following this release was reduced in the antisense-transfected cells compared with controls. It is concluded that PMCA1 is involved in neurite extension and/or stabilization either through moderation of local calcium levels, or by some other mechanism.