Role of the extracellular domain of FcεRIα in intracellular processing and surface expression of the high affinity receptor for IgE FcεRI

Role of the extracellular domain of FcεRIα in intracellular processing and surface expression of the high affinity receptor for IgE FcεRI
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DOI:
10.1016/j.molimm.2007.11.017
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发表时间:
2008-04-01
影响因子:
3.6
通讯作者:
Kinet, Jean-Pierre
Kinet, Jean-Pierre
中科院分区:
医学3区
文献类型:
--
作者:
Hartman, Mor-Li;Lin, Shih-Yao;Kinet, Jean-Pierre

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免疫球蛋白 E 的高亲和力受体 Fc epsilon RI 是 IgE 介导的过敏反应的关键成分。它表达为由 IgE 结合 α 链和由 β 链和 γ 链二聚体形成的信号模块组成的四聚体(α beta gamma 2)。它在人类和啮齿动物的嗜碱性粒细胞和肥大细胞中以高水平表达,并且在激活后,它会诱导过敏介质的释放。在人类中也存在缺乏β链的三聚体形式(αβγ2)。这种三聚体形式在抗原呈递细胞上表达,通过 IgE 促进抗原呈递。三聚体的表达和信号传导能力均低于四聚体。人类(四聚体和三聚体)和小鼠(仅四聚体)表达之间的差异部分可以解释为:在缺乏β的情况下,小鼠α不能在细胞表面表达,而人类α可以。在这里,我们证明了人类α在缺乏β的情况下在细胞表面表达的能力完全是在其细胞外结构域中编码的。这些发现表明,I 型跨膜蛋白 Fc epsilon RI α 的胞外结构域在 Fc epsilon RI 细胞内加工和细胞表面表达中发挥作用。 (C) 2007 Elsevier Ltd. 保留所有权利。
The high affinity receptor for immunoglobulin E, Fc epsilon RI, is a critical component of IgE-mediated allergic reactions. It is expressed as a tetrarner (alpha beta gamma 2) made of an IgE-binding alpha chain and a signaling module formed by the beta chain and a dimer of gamma chains. It is expressed in humans and rodents on basophils and mast cells at a high level, and, upon activation, it induces the liberation of allergy mediators. In humans a trimeric form lacking the beta chain also exists (alpha beta gamma 2). This trimeric form is expressed on antigen presenting cells where it acts to facilitate antigen presentation via IgE. Both the expression and the signaling capacity of the trimer are lower than those of the tetramer. The differences between human (tetrameric and trimeric) and murine (tetrameric only) expression is explained in part by the fact that mouse alpha cannot be expressed at the cell surface in the absence of beta, while human alpha can. Here we demonstrate that the capacity of human a to be expressed at the cell surface in the absence of beta is encoded entirely in its extracellular domain. These findings show that the extracellular domain of the type I transmernbrane protein Fc epsilon RI alpha plays a role in Fc epsilon RI intracellular processing and expression at the cell surface. (C) 2007 Elsevier Ltd. All rights reserved.