THE HUMAN AROMATIC L-AMINO-ACID DECARBOXYLASE GENE CAN BE ALTERNATIVELY SPLICED TO GENERATE UNIQUE PROTEIN ISOFORMS

Aromatic L-amino acid decarboxylase (AADC) is expressed in a wide vari ety of tissues, including those where it is known to convert L-DOPA an d 5-hydroxytryptophan to dopamine and serotonin, respectively. AADC ha s been cloned from many species and shown to undergo alternative splic ing within its 5' untranslated region. Here, we report that the human AADC gene can undergo additional alternative splicing of exon 3, gener ating two different protein isoforms (termed AADC(480) and AADC(442)). Both transcripts are widely expressed, with AADC(442) predominating i n many neuronal and nonneuronal tissues. When homogenates were prepare d from COS-7 cells transfected with expression vectors containing eith er cDNA, AADC(480) catalyzed the decarboxylation of both L-DOPA and 5- hydroxytryptophan. AADC(442) was inactive in either assay. These findi ngs suggested that AADC(442) may have a different function in non-mono amine-expressing tissues. Taken together, these results suggest that t he human AADC gene undergoes complex processing, leading to the format ion of both tissue-specific transcripts as well as unique protein isof orms.