Phosphatidylcholine: paving the way to neuronal differentiation

PAOLETTI, L,ELENA, C,MARCUCCI H AND BANCHIO, C

Banff

Congreso; ASBMB, ICBL; 2012

Phosphatidylcholine: paving the way to neuronal differentiation. Neuritogenesis is a dynamic process, involving the generation and extension of long protrusions called neurites and axons. This process is critically dependent on membrane biosynthesis. Phosphatidylcholine (PC) is the most abundant phospholipid in eukaryotic cells. During retinoic acid (RA) induced differentiation of neuroblastoma cells, the augmented PC synthesis is supported by the sequential activation of two enzymes of the Kennedy pathway: choline kinase (CK) and CDP:phosphocholine cytydilyltransferase alpha (CCTa). In addition, enforced CK or CCTa expression promoted neuronal differentiation even in the absence of RA. Interestingly, we found that the addition of PC liposomes promotes neuronal differentiation by activating ERK signaling cascade, mimicking RA effects. In addition, PC-treated neurons express bIII-tubulin as a differentiation marker. In light of these results, chemical inhibitors or siRNAs designed to specifically inhibit CK or CCTa activity, significantly abrogate the neuritogenesis process affecting also de expression of differentiation markers like bIII tubulin. Moreover, the activation of ERK signaling cascade is attenuated.