Nuclear c-Fos triggers neuritogenesis in PC 12 cells. Cytoplasmic c-Fos sustains neurite elongation.

GIL G,; BUSSOLINO D,; PORTAL M,; RENNER M,; BORIOLI G,; MARIO EDUARDO GUIDO; CAPUTTO BL,

AMER SOC CELL BIOLOGY

Año: 2004 vol. 15 p. 1881 - 1881

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