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 variety of tissues, including those where it is known to convert L-DOPA and 5-hydroxytryptophan to dopamine and serotonin, respectively. AADC has been cloned from many species and shown to undergo alternative splicing within its 5' untranslated region. Here, we report that the human AADC gene can undergo additional alternative splicing of exon 3, generating two different protein isoforms (termed AADC480 and AADC442). Both transcripts are widely expressed, with AADC442 predominating in many neuronal and nonneuronal tissues. When homogenates were prepared from COS-7 cells transfected with expression vectors containing either cDNA, AADC480 catalyzed the decarboxylation of both L-DOPA and 5-hydroxytryptophan. AADC442 was inactive in either assay. These findings suggested that AADC442 may have a different function in non-monoamine-expressing tissues. Taken together, these results suggest that the human AADC gene undergoes complex processing, leading to the formation of both tissue-specific transcripts as well as unique protein isoforms.
O'Malley
K L
KL
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Harmon
S
S
Moffat
M
M
Uhland-Smith
A
A
Wong
S
S
D006916:5-Hydroxytryptophan / Q000378:metabolism; D017398:Alternative Splicing; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D004274:DNA, Recombinant; D006801:Humans; D007536:Isomerism; D007700:Kinetics; D007980:Levodopa / Q000378:metabolism; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013379:Substrate Specificity; D014018:Tissue Distribution
D004274:DNA, Recombinant; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D007980:Levodopa; D006916:5-Hydroxytryptophan; D001142:Aromatic-L-Amino-Acid Decarboxylases