Phosphatidylcholine biosynthesis and neuronal differentiation

BANCHIO CLAUDIA; MARCUCCI HEBE; SUZANNE JACKOWSKI

Boston (EEUU)

Conferencia; Gordon Research Conference. Molecular and Cellular Biology of Lipids; 2007

Neuronal differentiation is a complex process characterized by a halt in proliferation and extension of neurites from the cell body. Changes in gene expression mediate the metabolic redirection leading to neurite formation and function. Acceleration of membrane phospholipid synthesis is associated with neurite elongation and phosphatidylcholine (PtdCho) is the major membrane phospholipid in mammalian cells. Our results indicate that membrane biogenesis is driven by the elevated expression of a subset of lipid biosynthetic genes following retinoic acid (RA)-induced differentiation of Neuro2A cells. The transcription of genes encoding key enzymes in the CDP-choline pathway of phospholipids biosynthesis is stimulated, including the Chka gene for choline kinase (CK) and the Pcyt1a gene for the CTP:phosphocholine cytidylyltransferase (CCT). The promoter regions for both genes indicated common DNA sequences which are proposed to be binding sites for transcription factors (TFs) that coordinately activate expression in a RA-dependent manner.  Alteration of CK or CCT expression by siRNA or overexpression regulated PtdCho synthesis and neurite extension following RA treatment.  These results indicate that PtdCho synthesis is necessary for RA-dependent differentiation of Neuro2A cells.