Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
EMBO J. 2011 Jan 5;30(1):205-20. doi: 10.1038/emboj.2010.290. Epub 2010 Nov 19.
By using differential display PCR, we have previously identified 98 cDNA fragments from rat dorsal hippocampus, which are expressed differentially between the fast learners and slow learners from water-maze learning task. One cDNA fragment, which showed a higher expression level in fast learners, encodes the rat protein inhibitor of activated STAT1 (pias1) gene. Spatial training induced a significant increase in PIAS1 expression in rat hippocampus. Transient transfection of the wild-type (WT) PIAS1 plasmid to CA1 neurons facilitated, whereas transfection of PIAS1 siRNA impaired spatial learning in rats. Meanwhile, PIAS1WT increased STAT1 sumoylation, decreased STAT1 DNA binding and decreased STAT1 phosphorylation at Tyr-701 associated with spatial learning facilitation. But PIAS1 siRNA transfection produced an opposite effect on these measures associated with spatial learning impairment. Further, transfection of STAT1 sumoylation mutant impaired spatial acquisition, whereas transfection of STAT1 phosphorylation mutant blocked the impairing effect of PIAS1 siRNA on spatial learning. In this study, we first demonstrate the role of PIAS1 in spatial learning. Both posttranslational modifications (increased sumoylation and decreased phosphorylation) mediate the effect of PIAS1 on spatial learning facilitation.
通过使用差异显示 PCR，我们先前从大鼠背海马体中鉴定出 98 个 cDNA 片段，这些片段在水迷宫学习任务中快速学习者和慢速学习者之间的表达存在差异。一个 cDNA 片段在快速学习者中表达水平较高，编码大鼠蛋白激活 STAT1 抑制剂 (pias1) 基因。空间训练诱导大鼠海马体中 PIAS1 表达显著增加。野生型 (WT) PIAS1 质粒瞬时转染 CA1 神经元促进空间学习，而 PIAS1 siRNA 转染则损害大鼠的空间学习。同时，PIAS1WT 增加 STAT1 泛素化，降低 STAT1 DNA 结合并降低与空间学习促进相关的 STAT1 磷酸化 Tyr-701。但 PIAS1 siRNA 转染对这些与空间学习损伤相关的措施产生了相反的影响。此外，STAT1 泛素化突变体的转染损害了空间获得，而 STAT1 磷酸化突变体的转染则阻断了 PIAS1 siRNA 对空间学习损伤的影响。在这项研究中，我们首次证明了 PIAS1 在空间学习中的作用。两种翻译后修饰（增加的泛素化和减少的磷酸化）介导了 PIAS1 对空间学习促进的作用。
