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Evidence of nuclear transport mechanisms in the protozoan parasite Giardia lamblia.
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ( IF 4.6 ) Pub Date : 2019-10-29 , DOI: 10.1016/j.bbamcr.2019.118566 Gonzalo Federico Mayol 1 , María Victoria Revuelta 1 , Agostina Salusso 1 , María Carolina Touz 1 , Andrea Silvana Rópolo 1
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ( IF 4.6 ) Pub Date : 2019-10-29 , DOI: 10.1016/j.bbamcr.2019.118566 Gonzalo Federico Mayol 1 , María Victoria Revuelta 1 , Agostina Salusso 1 , María Carolina Touz 1 , Andrea Silvana Rópolo 1
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Nuclear-cytoplasmic trafficking of proteins is a highly regulated process that modulates multiple biological processes in eukaryotic cells. In Giardia lamblia, shuttling has been described from the cytoplasm to nuclei of proteins during the biological cell cycle of the parasite. This suggests that a mechanism of nucleocytoplasmic transport is present and functional in G. lamblia. By means of computational biology analyses, we found that there are only two genes for nuclear transport in this parasite, named Importin α and Importin β. When these transporters were overexpressed, both localized close to the nuclear envelope, and no change was observed in trophozoite growth rate. However, during the encystation process, both transporters induced an increase in the number of cysts produced. Importazole and Ivermectin, two known specific inhibitors of importins, separately influenced the encysting process by inducing an arrest in the trophozoite stage that prevents the production of cysts. This effect was more noticeable when Ivermectin, an anti-parasitic drug, was used. Finally, we tested whether the enzyme arginine deiminase, which shuttles from the cytoplasm to the nuclei during encystation, was influenced by these transporters. We found that treatment with each of the inhibitors abrogates arginine deiminase nuclear translocation and favors perinuclear localization. This suggests that Importin α and Importin β are key transporters during the encystation process and are involved, at least, in the transport of arginine deiminase into the nuclei. Considering the effect produced by Ivermectin during growth and encystation, we postulate that this drug could be used to treat giardiasis.
中文翻译：
原生动物寄生虫贾第鞭毛虫兰伯核中核转运机制的证据。
蛋白质的核细胞质运输是一个高度调控的过程，可调节真核细胞中的多个生物学过程。在兰氏贾第鞭毛虫中，已经描述了在寄生虫的生物细胞周期期间从细胞质到蛋白核的穿梭。这表明在兰氏假丝酵母中存在核细胞质运输的机制并起作用。通过计算生物学分析，我们发现该寄生虫中只有两个用于核转运的基因，分别为Importinα和Importinβ。当这些转运蛋白过表达时，它们都位于核膜附近，并且滋养体的生长速率未见变化。但是，在侵入过程中，两种转运蛋白均导致产生的囊肿数量增加。进口唑和伊维菌素，两种重要的importins特异抑制剂通过诱导滋养体阶段的阻止而阻止了囊肿的产生，从而分别影响进入过程。当使用抗寄生虫药物伊维菌素时，这种作用更为明显。最后，我们测试了在转运过程中从细胞质穿梭到细胞核的精氨酸脱亚氨酶是否受这些转运蛋白的影响。我们发现，用每种抑制剂治疗都可消除精氨酸脱亚氨酶的核易位，并有利于核周定位。这表明Importinα和Importinβ是融合过程中的关键转运蛋白，至少参与了精氨酸脱亚氨酶向细胞核的转运。考虑到伊维菌素在生长和侵染过程中产生的作用，
更新日期：2019-10-29
中文翻译：
原生动物寄生虫贾第鞭毛虫兰伯核中核转运机制的证据。
蛋白质的核细胞质运输是一个高度调控的过程，可调节真核细胞中的多个生物学过程。在兰氏贾第鞭毛虫中，已经描述了在寄生虫的生物细胞周期期间从细胞质到蛋白核的穿梭。这表明在兰氏假丝酵母中存在核细胞质运输的机制并起作用。通过计算生物学分析，我们发现该寄生虫中只有两个用于核转运的基因，分别为Importinα和Importinβ。当这些转运蛋白过表达时，它们都位于核膜附近，并且滋养体的生长速率未见变化。但是，在侵入过程中，两种转运蛋白均导致产生的囊肿数量增加。进口唑和伊维菌素，两种重要的importins特异抑制剂通过诱导滋养体阶段的阻止而阻止了囊肿的产生，从而分别影响进入过程。当使用抗寄生虫药物伊维菌素时，这种作用更为明显。最后，我们测试了在转运过程中从细胞质穿梭到细胞核的精氨酸脱亚氨酶是否受这些转运蛋白的影响。我们发现，用每种抑制剂治疗都可消除精氨酸脱亚氨酶的核易位，并有利于核周定位。这表明Importinα和Importinβ是融合过程中的关键转运蛋白，至少参与了精氨酸脱亚氨酶向细胞核的转运。考虑到伊维菌素在生长和侵染过程中产生的作用，
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