Liu Haixiong, Wang Zhiqiang, Li Shifeng, Zhang Yunbin, Yan Yuan-Chang, Li Yi-ping
Shanghai Key Laboratory for Molecular Andrology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Yue Yang Road, Shanghai, 200031, China.
Mol Biol Rep. 2009 Jul;36(6):1469-74. doi: 10.1007/s11033-008-9337-x. Epub 2008 Aug 30.
Glutamate decarboxylase (GAD) is the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), the most important inhibitory neurotransmitter in central nervous system (CNS). Two homologous forms of GAD encoded by separate genes have been identified in mammalian brain, with molecular weight of 65 kDa (GAD65) and 67 kDa (GAD67). In the present study, four novel GAD67 transcripts produced by alternative splicing and polyadenlyation were cloned from rat testis. These novel GAD67 transcripts were widely expressed in non-neuronal tissues. During rat testis maturation, their expression level showed a time dependent change. These transcripts were predicted to synthesis of GAD proteins truncated of the binding site for pyridoxal phosphate, an essential cofactor, therefore cannot function as a decarboxylase. Thus, post-transcriptional processing mechanism as alternative splicing and polyadenlyation may play a crucial role in regulating rat GAD67 gene expression.
谷氨酸脱羧酶（GAD）是γ-氨基丁酸（GABA）合成中的限速酶，GABA是中枢神经系统（CNS）中最重要的抑制性神经递质。在哺乳动物大脑中已鉴定出由不同基因编码的两种同源形式的GAD，分子量分别为65 kDa（GAD65）和67 kDa（GAD67）。在本研究中，从大鼠睾丸中克隆了通过可变剪接和多聚腺苷酸化产生的四种新型GAD67转录本。这些新型GAD67转录本在非神经组织中广泛表达。在大鼠睾丸成熟过程中，它们的表达水平呈现出时间依赖性变化。预计这些转录本会合成截短了磷酸吡哆醛（一种必需辅因子）结合位点的GAD蛋白，因此不能作为脱羧酶发挥作用。因此，可变剪接和多聚腺苷酸化等转录后加工机制可能在调节大鼠GAD67基因表达中起关键作用。
