C-FOS REGULATES BRANCHING FORMATION IN NEURONS

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

Rosario

Congreso; L Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2014

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Neuronal differentiation is a complex event where lipid synthesis for membrane biogenesis plays a key role. As we have previously shown that c-Fos associates to membranes of the endoplasmic reticulum (ER) and activates phospholipid synthesis, it might be associated with the molecular mechanisms that allow the higher rate of membrane genesis required for neuronal differentiation. When c-Fos expression is blocked in primary cultures of rat hippocampal neurons, either using a lentiviral vector that expresses a specific sequence against c-Fos or a specific antibody, differentiation was impaired and no development of axonal processes was observed. Besides, analysis of c-Fos localization by immunofluorescence shows it co-localizing with ER markers in the neuronal soma and mainly forming structures at the branching sites of the neuronal processes. We checked if CTP:phosphocholine cytidylyltransferase-β2 (CCTβ2), an integral enzyme of the ER membranes that plays an important role in the formation of axon branches, could be activated by c-Fos. We observed co-immunoprecipitation of c-Fos with the enzyme and FRET technique has given positive results for the interaction between these two proteins, indicating a possible mechanism for branching regulation and supporting our hypothesis of the importance of c-Fos mediated activation of phospholipid synthesis during neuronal differentiation