c-Fos Activated Phospholipid Synthesis Is Required for Neurite Elongation in Differentiating PC12 Cells

G. A. GIL, D. F. BUSSOLINO, M. M. PORTAL, A. A. PECCHIO, M. L. RENNER, G. A. BORIOLLI, M. E. GUIDO AND B. L. CAPUTTO

MOLECULAR BIOLOGY OF THE CELL

AMER SOC CELL BIOLOGY

Año: 2004 vol. 15 p. 1881 - 1881

1059-1524

e have previously shown that c-Fos activates phospholipid synthesis through a mechanism independent of its genomic AP-1 activity. Herein, using PC12 cells induced to differentiate by nerve growth factor, the genomic effect of c-Fos in initiating neurite outgrowth is shown as distinct from its nongenomic effect of activating phospholipid synthesis and sustaining neurite elongation. Blocking c-Fos expression inhibited differentiation, phospholipid synthesis activation, and neuritogenesis. In cells primed to grow, blocking c-Fos expression determined neurite retraction. However, transfected cells expressing c-Fos or c-Fos deletion mutants with capacity to activate phospholipid synthesis sustain neurite outgrowth and elongation in the absence of nerve growth factor. Results disclose a dual function of c-Fos: it first releases the genomic program for differentiation and then associates to the endoplasmic reticulum and activates phospholipid synthesis. Because phospholipids are key membrane