Role of c-Fos in neuronal differentiation

RODRÍGUEZ, L; FERRERO, GO; CARDOZO-GIZZI, AM; CAPUTTO, BL

Córdoba

Congreso; LII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2016

The oncoprotein c-Fos is a well-recognized member of the AP-1 family of transcription factors. In addition to this canonical activity we have previously shown that cytoplasmic c-Fos activates phospholipid synthesis by its association with particular lipid synthesizing enzymes at the endoplasmic reticulum. This particular function might be associated with the molecular mechanisms that allow the higher rate of membrane genesis required for the complex events that take place during neuronal differentiation. In our aim to study the role of c-Fos during neuronal differentiation, we found a strong co-localization with ER markers in specific structures at branching sites of neuronal processes. Blocking either c-Fos expression or its activity provoked an impairment in differentiation with no development of axonal processes. As CCTβ2, an integral enzyme of the ER membranes that plays an important role in the formation of axon branches, has been shown to play a main role in axonal branching, we checked if it could be activated by c-Fos. We observed co-immunoprecipitation of c-Fos with the enzyme and a physical association between these two proteins as determined by FRET, indicating a possible mechanism for branching regulation. These results support our hypothesis that c-Fos mediated activation of phospholipid synthesis participates in neuronal differentiation.