Wang Bingwei, Li Zhihua, Xu Lei, Goggi Julian, Yu Yi, Zhou Jiawei
Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Gene. 2004 Apr 28;331:149-57. doi: 10.1016/j.gene.2004.02.009.
Dopamine denervation in the striata of patients with Parkinson's disease (PD) leads to changes in neural plasticity. However, the mechanisms leading to the changes are still poorly understood. In an effort to study the molecular events in the denervated striatum, we identified and cloned rat karyopherin alpha 1 (KPNA1), a member of the importin/karyopherin alpha (KPNA) family. DNA sequence analysis revealed that the full-length cDNA, encoding rat KPNA1, was 4975 bp with a short 5'-untranslated region (UTR) of 70 bp, a putative coding sequence of 1617 bp, and an unusually long 3'-UTR of 3266 bp. The gene shared a high degree of similarity with its mouse and human homologs at both cDNA and protein levels. By computational analysis of its genomic sequence, the transcription unit was shown to span a 44-kb region and consist of 13 exons varying in size from 89 (6th exon) to 3454 bp (13th exon), and 12 introns varying in size from 0.3 to 8.9 kb. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis demonstrated that KPNA1 transcript existed in various adult tissues. Both Northern blot and semi-quantitative RT-PCR analysis showed that the expression level of KPNA1 mRNA was altered in the denervated striatum post-lesion in a time-dependent manner, reaching the maximum at 2 weeks post-lesion. Our results suggest involvement of KPNA1 in the striatal responses to denervation following 6-hydroxydopamine (6-OHDA)-induced lesion.
帕金森病（PD）患者纹状体中的多巴胺去神经支配会导致神经可塑性发生变化。然而，导致这些变化的机制仍知之甚少。为了研究去神经支配纹状体中的分子事件，我们鉴定并克隆了大鼠核转运蛋白α1（KPNA1），它是输入蛋白/核转运蛋白α（KPNA）家族的成员。DNA序列分析显示，编码大鼠KPNA1的全长cDNA为4975 bp，具有70 bp的短5'非翻译区（UTR）、1617 bp的推定编码序列和3266 bp的异常长的3'UTR。该基因在cDNA和蛋白质水平上与其小鼠和人类同源物具有高度相似性。通过对其基因组序列的计算分析，转录单元显示跨越44 kb区域，由13个外显子组成，大小从89 bp（第6外显子）到3454 bp（第13外显子）不等，以及12个内含子，大小从0.3到8.9 kb不等。逆转录聚合酶链反应（RT-PCR）分析表明，KPNA1转录本存在于各种成年组织中。Northern印迹和半定量RT-PCR分析均表明，KPNA1 mRNA的表达水平在损伤后去神经支配的纹状体中呈时间依赖性改变，在损伤后2周达到最大值。我们的结果表明，KPNA1参与了6-羟基多巴胺（6-OHDA）诱导损伤后纹状体对去神经支配的反应。
