N-Glycosylation of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) Determines Its Trafficking and Stability and Is Required for Hepatitis B Virus Infection.
N-Glycosylation of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) Determines Its Trafficking and Stability and Is Required for Hepatitis B Virus Infection.
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Na+ - taurochaly共转运多肽（NTCP）的N-糖基化决定了其运输和稳定性，并且是乙型肝炎病毒感染所必需的。
DOI：
10.1371/journal.pone.0170419
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
van de Graaf SF
中科院分区：
文献类型：
--
作者：
Appelman MD;Chakraborty A;Protzer U;McKeating JA;van de Graaf SF
钠/胆汁酸协同转运蛋白NTCP最近被鉴定为B型肝炎病毒（HBV）的受体。NTCP是糖基化的，聚糖在蛋白质运输或病毒受体活性中的作用尚不清楚。NTCP含有两个N-连接的糖基化位点，并且天冬酰胺氨基酸残基N5和N11突变为谷氨酰胺以产生具有单个聚糖（NTCP-N5 Q或NTCP-N11 Q）或不具有聚糖（NTCP- N5，11 Q）的NTCP。表达具有单个聚糖的NTCP的HepG 2细胞以与NTCP-WT相当的水平支持HBV感染。在表达这些单一糖基化变体的细胞中，NTCP的生理功能（胆汁酸的摄取）也不受影响，这与它们向质膜的运输一致。然而，糖基化缺陷的NTCP（NTCP-N5，11 Q）未能支持HBV感染，表现出最小的细胞表达，并在溶酶体中降解。这以类似的方式影响NTCP-N5，11 Q的生理胆汁酸转运蛋白功能。总之，N-糖基化是NTCP在质膜上有效定位和随后的HBV感染所必需的，并且这些特征在携带单个碳水化合物部分的NTCP中得以保留。
The sodium/bile acid cotransporter NTCP was recently identified as a receptor for hepatitis B virus (HBV). NTCP is glycosylated and the role of glycans in protein trafficking or viral receptor activity is not known. NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). HepG2 cells expressing NTCP with a single glycan supported HBV infection at a comparable level to NTCP-WT. The physiological function of NTCP, the uptake of bile acids, was also not affected in cells expressing these single glycosylation variants, consistent with their trafficking to the plasma membrane. However, glycosylation-deficient NTCP (NTCP-N5,11Q) failed to support HBV infection, showed minimal cellular expression and was degraded in the lysosome. This affected the physiological bile acid transporter function of NTCP-N5,11Q in a similar fashion. In conclusion, N-glycosylation is required for efficient NTCP localization at the plasma membrane and subsequent HBV infection and these characteristics are preserved in NTCP carrying a single carbohydrate moiety.