Phospholipase D1 activity is involved in neuronal differentiation of immortalized hippocampal cell line

Abstract

To elucidate signal transduction pathways leading to neuronal differentiation, we have investigated a conditionally immortalized cell line from rat hippocampal neurons (H19-7) that expresses a temperature-sensitive simian virus 40 large T antigen. Treatment of H19-7 cells with the differentiating agent basic fibroblast growth factor (bFGF) at 39℃, the nonpermissive temperature for T function, resulted in the activation of Phospholipase D1 (PLD). Phospholipase D (PLD) is widely distributed in mammalian cells and implicated in a variety of physiological processes that reveal it to be a member of the signal transducing phospholipasees. To investigate the role of PLD1 in neuronal differentiation, we have examined bFGF-induced PLD1 activation is markedly induced during the differentiation of H19-7 cells. A dominant-negative mutant of PLD1and2 blocked bFGF-induced PLD activity as well as bFGF-induced neuronal differentiation. Elevated expression of PLD1 in the H19-7 cells led to neuronal differentiation in the absence of bFGF. These results suggest that PLD1 activation is important in the neuronal differentiation of central nervous system hippocampal cells.