Abstract
Catecholaminergic (dopaminergic, noradrenergic, and adrenergic) transmitter phenotypes require the cooperative actions of four biosynthetic enzymes: tyrosine hydroxylase, aromatic L-amino acid decarboxylase, dopamine beta-hydroxylase, and phenylethanolamine N-methyltransferase. Mechanisms that control expression of these enzymes in a transmitter phenotype-specific manner, however, are poorly understood. Here, we provide evidence that overexpression of a novel cdc10/SWI6 motif-containing protein, V-1, elicits the coordinate up-regulation of tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and dopamine beta-hydroxylase mRNAs in the neuronal cell line PC12D, and as a result, catecholamine levels are increased. Furthermore, V-1 is strongly expressed in the cytoplasm of rat chromaffin cells of adrenal medulla. Thus, V-1 may act as a cytoplasmic protein/protein adapter and be involved in control of the catecholaminergic phenotype expression via an intracellular pathway signaling to the nucleus.
Highlights
Abnormalities in catecholamine biosynthesis and neurotransmission have been implicated as the cause of neurological and psychiatric diseases [1]
Mash1 and Phox2 transcription factors have been recently shown by gene targeting to be required for development of subpopulations of central nervous system and peripheral nervous system catecholaminergic neurons [18, 19]
Expression of V-1 mRNA gradually increases to reach a maximal level during the first to second postnatal weeks, declining thereafter to adult levels by postnatal day 28.2 strong expression of the V-1 gene persists in regions of synaptic plasticity even after the second postnatal week [24]
Summary
Abnormalities in catecholamine biosynthesis and neurotransmission have been implicated as the cause of neurological and psychiatric diseases [1]. Levels of the larger AADC mRNA species were increased 20.2– 68.2-fold in V-1-overexpressing clones compared with those of the control clones, where AADC mRNA expression appeared to be down-regulated in comparison with that of parent cell (Fig. 3, A and B).3 Three mRNA species of the third enzyme DBH were detected in all transfectants.
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