Role of phosphatidylcholine during neuronal differentiation

PAOLETTI, L Y BANCHIO C

Mendoza

Congreso; SAIB; 2012

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 has 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 LPC. In fact,  PC derivative metabolites like  lysophosphatidylcholine, 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.