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J. Biol. Chem. 285 (33): 25382-25393

© 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

Phosphatidylcholine Biosynthesis during Neuronal Differentiation and Its Role in Cell Fate Determination*Formula

Hebe Marcucci{ddagger}1, Luciana Paoletti{ddagger}1, Suzanne Jackowski§, , and Claudia Banchio{ddagger}2

From the {ddagger}Instituto de Biología Molecular y Celular de Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas, Departamento de Ciencias Biológicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario, Argentina and
the §Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-3678

ABSTRACT Back to Top

Abstract: Neuronal differentiation is characterized by neuritogenesis and neurite outgrowth, processes that 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 {alpha} (CK{alpha}) and choline cytidylyltransferase {alpha} (CCT{alpha}). Early after RA stimulation, the increase in PtdCho synthesis is mainly governed by the biochemical activation of CCT{alpha}. Later, the transcription of CK{alpha}- and CCT{alpha}-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 CK{alpha} or CCT{alpha} 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 CCT{alpha} or CK{alpha} was dependent on persistent ERK activation. These results indicate that elevated PtdCho synthesis could mimic the RA signals and thus determine neuronal cell fate. Moreover, they could explain the key role that PtdCho plays during neuronal regeneration.

Key Words: Mitogen-activated Protein Kinases (MAPKs) • Membrane Lipids • Neurodifferentiation • Neurotrophic Factor • Phosphatidylcholine

Received for publication April 29, 2010. Revision received June 3, 2010.


1 Both authors contributed equally to this work.

2 To whom correspondence should be addressed. Tel.: 54-341-4350661; Fax: 54-341-4804601; E-mail: banchio{at}

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