IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
artículos
Título:
Phosphatidylcholine Biosynthesis during Neuronal Differentiation and Its Role in Cell Fate Determination
Autor/es:
MARCUCCI H.*-PAOLETTI L.*, SUZANNE JACKOWSKI, BANCHIO C.
Revista:
JOURNAL OF BIOLOGICAL CHEMISTRY
Editorial:
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Referencias:
Año: 2010 vol. 285 p. 25382 - 25393
ISSN:
0021-9258
Resumen:
Neuronal differentiation is characterized by neuritogenesis and neurite outgrowth, processes which are dependent on membrane biosynthesis. Thus, the production of phosphatidylcholine (PtdCho), the major membrane phospholipid, should be stimulated during neuronal differentiation. We demonstrate that during retinoic acid (RA)-induced differentiation of Neuro-2a cells, PtdCho synthesis was promoted by an ordered and sequential activation of choline kinase á (CKa) and choline cytidylyltransferase a (CCTa). Early after RA stimulation, the increase in PtdCho synthesis is governed by the biochemical activation of CCTa. Later, the transcription of CKa and CCTa encoding genes was induced. Both, PtdCho biosynthesis and neuronal differentiation are dependent on ERK activation. A novel mechanism is proposed by which PtdCho biosynthesis is coordinated during neuronal differentiation. Enforced expression of either CKa or CCTa increased the rate of synthesis and the amount of PtdCho, and these cells initiated differentiation without RA stimulation, as evidenced by cell morphology and the expression of genes associated with neuritogenesis. The differentiation resulting from enforced expression of CCTa or CKa was dependent on persistent ERK activation. These results indicate that elevated PtdCho synthesis could mimic the RA signals, and thus determining neuronal cell fate. Moreover, they could explain the key role that PtdCho plays during neuronal regeneration.