Functional characterization of the human-specific (type II) form of kallikrein 8, a gene involved in learning and memory
Functional characterization of the human-specific (type II) form of kallikrein 8, a gene involved in learning and memory
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激肽释放酶 8（一种参与学习和记忆的基因）的人类特异性（II 型）形式的功能表征
DOI：
10.1038/cr.2009.4
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发表时间：
2009-02-01
期刊：
影响因子：
44.1
通讯作者：
Su, Bing
中科院分区：
文献类型：
--
作者：
Lu, Zhi-Xiang;Huang, Qin;Su, Bing
激肽释放酶8（KLK 8）是一种丝氨酸蛋白酶，在中枢神经系统中发挥作用，并且在神经元活动的许多方面是必需的。不同灵长类物种之间的序列比较和基因表达分析确定了KLK 8（II型）的人类特异性剪接形式，在人脑中优先表达，这可能有助于人类认知的起源。为了深入了解这种新形式的生理和生化作用，我们对人类II型KLK 8进行了功能分析。我们的研究结果表明，II型KLK 8在人胚胎干细胞和胚胎脑样品中大量表达，表明在胚胎发生中的潜在作用。在不同的个体和脑区，其表达存在着显著的差异，这反映了其在神经活动中的动态作用。此外，KLK 8的转录起始位点（TSS）是组织特异性的，在人类中发现的脑特异性TSS表明功能特化。我们的体外生化分析表明，有一个II型特异性的中间蛋白质形式，虽然加工的终点酶是相同的I型和II型KLK 8，这表明II型KLK 8在人脑中的出现可能导致KLK 8的功能修饰。
Kallikrein 8 (KLK8) is a serine protease functioning in the central nervous system, and essential in many aspects of neuronal activities. Sequence comparison and gene expression analysis among diverse primate species identified a human-specific splice form of KLK8 (type II) with preferential expression in the human brain, which may contribute to the origin of human cognition. To gain insights into the physiological and biochemical role of this novel form, we conducted functional analyses of human type II KLK8. Our results show that type II KLK8 is abundantly expressed in human embryonic stem cells and in embryo brain samples, suggesting a potential role in embryogenesis. There are dramatic expression variations in different individuals and brain regions, which is a reflection of its dynamic role in neural activities. Furthermore, the transcription start site (TSS) of KLK8 is tissue-specific, with a brain-specific TSS found in humans indicating functional specialization. Our in vitro biochemical assay shows that there is a type II-specific intermediate protein form, although the processed end-point enzymes are the same for both type I and type II KLK8, suggesting that the emergence of type II KLK8 in the human brain likely leads to functional modifications of KLK8.