Endocytosis and recycling of varicella-zoster virus fc receptor glycoprotein gE: Internalization mediated by a YXXL motif in the cytoplasmic tail
Endocytosis and recycling of varicella-zoster virus fc receptor glycoprotein gE: Internalization mediated by a YXXL motif in the cytoplasmic tail
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DOI：
10.1128/jvi.71.5.4042-4054.1997
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发表时间：
1997-05-01
影响因子：
5.4
通讯作者：
Grose, C
中科院分区：
文献类型：
--
作者：
Olson, JK;Grose, C
水痘带状疱疹病毒（VZV）编码细胞表面Fc受体、糖蛋白gE，VZV gE此前已被证明显示出非病毒细胞表面受体常见的几种特征，最近，据报道VZV gE在二聚体形式上被酪氨酸磷酸化（J，K. Olson，G，A，Bishop和C，Grose，J，Virol，71：110-119，1997）。此后，注意力集中在VZV gE进行受体介导的内吞作用的能力上。目前的瞬时转染研究通过共聚焦显微镜和内化测定证明，当在HeLa细胞中表达时，VZV gE被内吞。gE的内吞作用显示依赖于细胞内网格蛋白包被的囊泡的形成。随后的共定位研究显示，VZV gE的内吞作用密切模拟转铁蛋白受体的内吞作用，通过诱变研究确定gE胞质尾区，更具体地说是酪氨酸残基582，对于蛋白质的有效内化是重要的;该酪氨酸残基是保守的YXXL基序的一部分，在任何给定时间内化的gE的量达到32%的稳定状态。此外，与转铁蛋白受体一样，内化的gE再循环到细胞表面。gE内吞作用的发现提供了对gE丝氨酸/苏氨酸和酪氨酸磷酸化的早期文献的了解，由于这些磷酸化事件可以作为内化受体的分选信号，结合先前发现人和猿免疫缺陷病毒包膜蛋白都可以经历内吞作用，gE发现提示包膜组分的内吞作用可能是不同包膜病毒家族中的翻译后调节机制，
Varicella-zoster virus (VZV) encodes a cell surface Fc receptor, glycoprotein gE, VZV gE has previously been shown to display several features common to nonviral cell surface receptors, Most recently, VZV gE was reported to be tyrosine phosphorylated on a dimeric form (J, K. Olson, G, A, Bishop, and C, Grose, J, Virol, 71:110-119, 1997), Thereafter, attention focused on the ability of VZV gE to undergo receptor-mediated endocytosis, The current transient transfection studies demonstrated by confocal microscopy and internalization assays that VZV gE was endocytosed when expressed in HeLa cells, Endocytosis of gE was shown to be dependent on clathrin-coated vesicle formation within the cells, Subsequent colocalization studies showed that endocytosis of VZV gE closely mimicked endocytosis of the transferrin receptor, The gE cytoplasmic tail and more specifically tyrosine residue 582 were determined by mutagenesis studies to be important for efficient internalization of the protein; this tyrosine residue is part of a conserved YXXL motif, The amount of gE internalized at any given time reached a steady state of 32%, In addition, like the transferrin receptor, internalized gE recycled to the cell surface, The finding of gE endocytosis provided insight into earlier documentation of gE serine/threonine and tyrosine phosphorylation, since these phosphorylation events may serve as sorting signals for internalized receptors, Taken together with the previous discovery that both human and simian immuno-deficiency virus envelope proteins can undergo endocytosis, the gE findings suggest that endocytosis of envelope components may be a posttranslational regulatory mechanism among divergent families of enveloped viruses,