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Originally published as MBC in Press, 10.1091/mbc.E03-09-0705 on February 6, 2004

Vol. 15, Issue 4, 1881-1894, April 2004

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

Germán A. Gil, Daniela F. Bussolino, Maximiliano M. Portal, Adolfo Alfonso Pecchio, Marianne L. Renner, Graciela A. Borioli, Mario E. Guido, and Beatriz L. Caputto *

Centro de Investigaciones en Química Biológica de Córdoba (Consejo Nacional de Investigaciones Científicas y Técnicas), Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, 5000 Córdoba, Argentina

Submitted September 30, 2003; Revised December 23, 2003; Accepted January 10, 2004
Monitoring Editor: Guido Guidotti

We 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 components, we hypothesize this latter phenomenon as crucial to support membrane genesis demands required for cell growth and neurite elongation.


Article published online ahead of print. Mol. Biol. Cell 10.1091/mbc.E03-09-0705. Article and publication date are available at www.molbiolcell.org/cgi/doi/10.1091/mbc.E03-09-0705.

Online version is available at www.molbiolcell.org.

Abbreviations used: A-Calp, acetyl calpastatin; ASO, antisense oligonucleotide; NLSP, nuclear localization signal peptide; SO, sense oligonucleotide.

Online version of this article contains supplementary material.

* Corresponding author. E-mail address: bcaputto{at}dqbfcq.uncor.edu.




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