Functional characterization of the human-specific (type Ⅱ)form of kallikrein 8, a gene involved in learning and memory

• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2009,（2）
• 页码范围: 259-267
• 页数: 9页
• 语种: 英文
• DOI: 10.1038/cr.2009.4

摘要

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 Ⅱspecific intermediate protein form, although the processed end-point enzymes are the same for both type I and type ⅡKLK8, suggesting that the emergence of type 11 KLK8 in the human brain likely leads to functional modifications of KLK8.