O'Malley K L, Harmon S, Moffat M, Uhland-Smith A, Wong S
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri, USA.
J Neurochem. 1995 Dec;65(6):2409-16. doi: 10.1046/j.1471-4159.1995.65062409.x.
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.
芳香族L-氨基酸脱羧酶（AADC）在多种组织中表达，包括已知其分别将L-多巴和5-羟色氨酸转化为多巴胺和5-羟色胺的组织。AADC已从许多物种中克隆出来，并显示在其5'非翻译区内发生可变剪接。在此，我们报告人类AADC基因可在外显子3处发生额外的可变剪接，产生两种不同的蛋白质异构体（称为AADC480和AADC442）。两种转录本均广泛表达，其中AADC442在许多神经元和非神经元组织中占主导地位。当用含有任一cDNA的表达载体转染的COS-7细胞制备匀浆时，AADC480催化L-多巴和5-羟色氨酸的脱羧反应。AADC442在任一检测中均无活性。这些发现表明，AADC442在不表达单胺的组织中可能具有不同的功能。综上所述，这些结果表明人类AADC基因经历复杂的加工过程，导致形成组织特异性转录本以及独特的蛋白质异构体。
