Nuclear Export Signal-Interacting Protein Forms Complexes with Lamin A/C-Nups To Mediate the CRM1-Independent Nuclear Export of Large Hepatitis Delta Antigen
Nuclear Export Signal-Interacting Protein Forms Complexes with Lamin A/C-Nups To Mediate the CRM1-Independent Nuclear Export of Large Hepatitis Delta Antigen
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DOI：
10.1128/jvi.02357-12
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发表时间：
2013-02-01
影响因子：
5.4
通讯作者：
Chang, Ming-Fu
中科院分区：
文献类型：
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作者：
Huang, Cheng;Jiang, Jia-Yin;Chang, Ming-Fu
核输出是一个重要的过程，它不仅调节细胞因子的功能，而且促进病毒核蛋白复合物的组装。染色体区域维持蛋白1（CRM 1）介导携带经典的富含亮氨酸的核输出信号（内斯）的蛋白质的转运，是最具特征的核输出受体。最近，几个CRM 1独立的核输出途径也被确定。大型丁型肝炎抗原（HDAg-L）是丁型肝炎病毒（HDV）的核衣壳蛋白，其含有CRM 1非依赖性富含脯氨酸的内斯，其核输出由宿主NES相互作用蛋白（NESI）介导。NESI蛋白介导核输出的机制尚不清楚。在这项研究中，NESI的特点是作为一个高度糖基化的膜蛋白。它与核纤层蛋白A/C和核孔蛋白相互作用并共定位于核膜中。重要的是，HDAg-L可以与核纤层蛋白A/C和核孔蛋白免疫共沉淀。此外，对于野生型蛋白，检测到货物HDAg-L与NESI的C末端的结合，但对于携带P205 A突变的核输出缺陷型HDAg-L [HDAg-L（P205 A）]，未检测到货物HDAg-L与NESI的C末端的结合。核纤层蛋白A/C的敲除有效地减少了HDAg-L的核输出和HDV的组装。这些数据表明，通过与核纤层蛋白A/C和核孔蛋白形成复合物，NESI促进了HDAg-L的CRM 1非依赖性核输出。
Nuclear export is an important process that not only regulates the functions of cellular factors but also facilitates the assembly of viral nucleoprotein complexes. Chromosome region maintenance 1 (CRM1) that mediates the transport of proteins bearing the classical leucine-rich nuclear export signal (NES) is the best-characterized nuclear export receptor. Recently, several CRM1-independent nuclear export pathways were also identified. The nuclear export of the large form of hepatitis delta antigen (HDAg-L), a nucleocapsid protein of hepatitis delta virus (HDV), which contains a CRM1-independent proline-rich NES, is mediated by the host NES-interacting protein (NESI). The mechanism of the NESI protein in mediating nuclear export is still unknown. In this study, NESI was characterized as a highly glycosylated membrane protein. It interacted and colocalized well in the nuclear envelope with lamin A/C and nucleoporins. Importantly, HDAg-L could be coimmunoprecipitated with lamin A/C and nucleoporins. In addition, binding of the cargo HDAg-L to the C terminus of NESI was detected for the wild-type protein but not for the nuclear export-defective HDAg-L carrying a P205A mutation [HDAg-L(P205A)]. Knockdown of lamin A/C effectively reduced the nuclear export of HDAg-L and the assembly of HDV. These data indicate that by forming complexes with lamin A/C and nucleoporins, NESI facilitates the CRM1-independent nuclear export of HDAg-L.