Role of c-Fos as an activator of phospholipid synthesis during neuronal differentiation

FERRERO, GABRIEL ORLANDO; CAPUTTO, BEATRIZ LEONOR; RODRÍGUEZ, LUCIA; CARDOZO-GIZZI, ANDRÉS MAURICIO

Zurich

Conferencia; 58th International Conference on the Bioscience of Lipids (ICBL); 2017

International Conference on the Bioscience of Lipids

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. CTP:phosphocholine cytidylyltransferase-β2 (CCTβ2) is an integral enzyme of the ER membranes that has been shown to play an important role in the formation of axon branches. To determine if this enzyme is activated by a c-Fos-dependent mechanism, and taking into consideration that this activation mechanism implies an interaction between both proteins, we initially studied this possible interaction. We observed co-immunoprecipitation of c-Fos with the enzyme and positive FRET values between the tagged proteins, both in the soma (ER) and in the axon of developing neurons, evidencing an interaction between these proteins. These results support the participation of CCTβ2 in the regulation of branching formation and sustain the notion that c-Fos mediated activation of phospholipid synthesis is of importance during neuronal differentiation.