Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 285, Issue 33, Pages 25382-25393Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.139477
Keywords
-
Categories
Funding
- Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Argentina
- Agencia de Promocion Cientifica y Tecnologica (ANPCyT), Argentina [PICT 01-38027]
- American Lebanese and Syrian Associated Charity
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available