Analysis of the Neuronal Promoter of the Rat Aromatic l‐Amino Acid Decarboxylase Gene

Abstract

The rat aromatic l‐amino acid decarboxylase (AADC) gene contains alternative promoters directing expression of neuronal and nonneuronal mRNAs that differ only in their 5′ untranslated regions (UTRs). We have analyzed the expression of the neuronal promoter of the AADC gene in cells synthesizing catecholamines and serotonin, as well as in non‐AADC‐expressing cells. We demonstrate the use of the neuronal‐specific UTR in individual dopamine‐, norepinephrine‐, and serotonin‐containing neurons. Transfection analyses show that the rat AADC neuronal promoter, containing 2,400 bp upstream of the transcription start site and including the 68‐bp untranslated exon 2, can activate transcription from a reporter gene in both catecholaminergic and serotonergic cell lines. These analyses identified several positive and negative cis‐active elements within this region. Unexpectedly, we observed that this promoter, when removed from its native context within the AADC gene, can also direct expression of a reporter gene in cells that do not normally express AADC mRNA. These results suggest that tissue‐specific expression of the neuronal promoter may not be controlled by cis‐active elements within the first 2,400 bp of the promoter. Additional information may be required to restrict neuronal promoter expression to appropriate cell types. This regulatory information could reside elsewhere within the promoter, within introns, or may be provided by interactions between the two AADC promoters.

Trace Amines and Their Receptors

“…As described above, AADC is found in both neuronal and non-neuronal cells and alternative splicing of exons 556 Gainetdinov et al 1 and 2 within the 59-untranslated region has been established as allowing for distinct control of neuronal and non-neuronal expression (Albert et al, 1992;Ichinose et al, 1992;Hahn et al, 1993;Sumi-Ichinose et al, 1995). A variety of transcription factor binding sites have been identified within both the neuronal (Chireux et al, 1994;Aguanno et al, 1995) and non-neuronal (Aguanno et al, 1996) promoter regions through which tissue-selective expression could occur. A variant on this alternative splicing, in which the non-neuronal variant was spliced to the neuronal acceptor site, has also been suggested in G cells of the rat stomach antrum (Djali et al, 1998), which may indicate cell type-selective plasticity in the control of AADC expression.…”

Enhancing Aromatic L‐amino Acid Decarboxylase Activity: Implications for L‐DOPA Treatment in Parkinson's Disease

“…Prolonged induction of AAAD (days) also occurs after chronic administration of neuroactive drugs [20]. Although the transcription of AAAD in neuronal cells is not fully explored, the presence of putative regulatory elements on the promoter [21–23] (Genbank AY37370) and the observation that pharmacological agents, hormones, and trophic factors change the abundance of AAAD mRNA [13,19,24–31] imply that the transcriptional regulation of the enzyme is possible. The finding that icv forskolin induces a late increase of AAAD activity and mRNA in midbrain neurons suggests that cyclic‐AMP might regulate the transcription of AAAD in vivo [10].…”

Regulation of the Cell-specific Calcitonin/Calcitonin Gene-related Peptide Enhancer by USF and the Foxa2 Forkhead Protein

“…Another neuronal and neuroendocrine Foxa2 target gene is the neuronal aromatic amino acid decarboxylase gene (41). Interestingly, this promoter is very active in the CA77 thyroid C cell line (42). Foxa2 is also induced during neuronal differentiation of P19 cells (43), and is expressed in the embryonic neural floor plate and ventral midline cells of the central nervous system (44).…”