Mutations in the cytoplasmic domain of the influenza virus hemagglutinin affect different stages of intracellular transport.
Mutations in the cytoplasmic domain of the influenza virus hemagglutinin affect different stages of intracellular transport.
复制标题
流感病毒血凝素的细胞质结构域的突变会影响细胞内转运的不同阶段。
DOI：
10.1083/jcb.100.3.704
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发表时间：
1985-03
影响因子：
7.8
通讯作者：
Gething, M J
中科院分区：
文献类型：
--
作者：
Doyle, C;Roth, M G;Sambrook, J;Gething, M J
在克隆的流感病毒血凝素（HA）编码DNA序列中引入了突变，并利用SV40-HA重组病毒载体在猿猴细胞中表达了由此产生的突变基因。在这项研究中，我们分析了透明质酸分子细胞质区域的特异性改变对其生物合成和运输速率、细胞定位和生物活性的影响。一些突变体在从内质网到细胞表面的运输途径中表现出异常。一个突变的HA留在内质网内；另一些在内质网核心糖基化完成后延迟到达高尔基体，但随后以正常速度从高尔基体进展到细胞表面；另一个在从高尔基体到质膜的运输中被延迟。然而，两个突变体从内质网通过高尔基体到细胞表面的移动速度与野生型HA没有区别。我们得出的结论是，细胞质结构域的变化可以有力地影响细胞内运输的速率和透明质酸到达细胞表面的效率。然而，对于感染细胞表面具有生物活性的透明质酸的成熟和有效表达来说，这一分子区域的绝对保守性并不是必需的。
Mutations have been introduced into the cloned DNA sequences coding for influenza virus hemagglutinin (HA), and the resulting mutant genes have been expressed in simian cells by the use of SV40-HA recombinant viral vectors. In this study we analyzed the effect of specific alterations in the cytoplasmic domain of the HA molecule on its rate of biosynthesis and transport, cellular localization, and biological activity. Several of the mutants displayed abnormalities in the pathway of transport from the endoplasmic reticulum to the cell surface. One mutant HA remained within the endoplasmic reticulum; others were delayed in reaching the Golgi apparatus after core glycosylation had been completed in the endoplasmic reticulum, but then progressed at a normal rate from the Golgi apparatus to the cell surface; another was delayed in transport from the Golgi apparatus to the plasma membrane. However, two mutants were indistinguishable from wild-type HA in their rate of movement from the endoplasmic reticulum through the Golgi apparatus to the cell surface. We conclude that changes in the cytoplasmic domain can powerfully influence the rate of intracellular transport and the efficiency with which HA reaches the cell surface. Nevertheless, absolute conservation of this region of the molecule is not required for maturation and efficient expression of a biologically active HA on the surface of infected cells.