Regulation of Chka expression during RA-induced neuronal differentiation. A major role for C/EBP.

DOMIZI, P. AND BANCHIO, C.

Potrero de los Funes

Congreso; SAIB; 2011

Neuronal differentiation is accompanied by changes in gene expression that mediate the 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. The transcription of two genes in particular encoding key enzymes in the CDP-choline pathway for PtdCho biosynthesis are stimulated; the Chka gene for choline kinase (CK) alpha isoform and the Pcyt1a gene for the CTP:phosphocholine cytidylyltransferase (CCT) alpha isoform. By analysis of reporter constructs we demonstrated that the increased binding of the transcription factor C/EBPb to the Chka-proximal promoter is in part responsible for the increased transcription during RA-induced differentiation of Neuro-2a cells. Besides, C/EBPb overexpression is able to induce CKa expression and promote neuronal differentiation.This is the first elucidation of the mechanism by which the expression of Chka is regulated during neuronal differentiation.