Role of phosphatidylcholine during neuronal differentiation

PAOLETTI L. Y BANCHIO C.

Mendoza

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Bioquímica y Biología Molecular; 2012

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Neuronal differentiation is a process that requires membrane biosynthesis. Phosphatidylcholine (PC), the most abundant phospholipid in membranes of eukaryotic cells, is mainly synthesized through the Kennedy pathway. During retinoic acid (RA) induced differentiation of neuroblastoma cells, PC synthesis is induced by increased expression of CTP:phosphocholine cytydilyltransferase alpha and choline kinase. We demonstrated that cell lines that overexpressed these enzymes have increased levels of PC and they undergo neuronal differentiation in the absence of RA. Interestingly, we found that the addition of PC liposomes promotes neuronal differentiation by activating ERK signalling cascade, mimicking the RA effects. In addition, we demonstrated that PC-induced differentiation is dependent of phospholipase A2 activity suggesting a role of lysophosphatidylcholine (LPC). In fact, PC derivative metabolites such as LPC, choline and phosphatidic acid (but not lysophosphatidic acid) induce neuronal differentiation. These results allow us to propose that PC, and derivative metabolites, are not only important structural membrane building blocks, but could also stimulate signalling pathways driving neuronal differentiation, which means a significant progress in the identification of specific signals regulating neuritogenesis.