c-Fos activated phospholipid synthesis is required for neurite elongation in differentiating PC12 cells.
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.
Gil
Germán A
GA
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.
Bussolino
Daniela F
DF
Portal
Maximiliano M
MM
Alfonso Pecchio
Adolfo
A
Renner
Marianne L
ML
Borioli
Graciela A
GA
Guido
Mario E
ME
Caputto
Beatriz L
BL
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D017353:Gene Deletion; D008856:Microscopy, Fluorescence; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D010743:Phospholipids / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry; D014162:Transfection
D010743:Phospholipids; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011994:Recombinant Proteins