Export of the high affinity IgE receptor from the endoplasmic reticulum depends on a glycosylation-mediated quality control mechanism
Export of the high affinity IgE receptor from the endoplasmic reticulum depends on a glycosylation-mediated quality control mechanism
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DOI：
10.4049/jimmunol.165.10.5686
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发表时间：
2000-11-15
影响因子：
4.4
通讯作者：
Robertson, MW
中科院分区：
文献类型：
--
作者：
Albrecht, B;Woisetschläger, M;Robertson, MW
高亲和力 IgE 受体 (Fc epsilon RI) 是由 alpha gamma (2) 或 alpha beta gamma (2) 链组成的多亚基复合物。 IgE 结合 α 链与 γ 链二聚体的共翻译组装以高度受控的方式发生，并且被认为涉及掩蔽存在于 Fc epsilon RI α 链细胞质 C 末端的二赖氨酸基序，该基序将该亚基定位到内质网 (ER)。在这里，我们表明 ER 质量控制调节新合成的 α γ (2) 和 ER 的输出alpha beta gamma (2) 受体，我们证明，FceRI α 链上存在未修剪的 N 连接核心聚糖 (Gle(3)Man(9)GleNAc(2)) 会激活 ER 质量控制机制，以在 ER 中保留该亚基，尽管存在 γ 链。同时，未修剪的 ER 定位 α 链表现出 IgE 结合活性，表明 Fc epsilon RI α链折叠发生在组成型葡萄糖修剪之前。在其他实验中，我们证明α链C端截短突变体的细胞表面表达也依赖于葡萄糖修剪，但不依赖于γ链共表达。我们认为，末端葡萄糖残基的葡萄糖苷酶修剪是 Fc epsilon RI α 从 ER 输出的关键控制步骤。最后，我们表明，在不存在其他 FceRI 亚基的情况下表达的组成型 ER FceRI α 链与 ER 凝集素样伴侣钙联蛋白结合，但不与结构相似的 ER 伴侣钙网蛋白结合，推测是通过与单糖基化 α 链 ER 糖型相互作用。
The high affinity IgE receptor (Fc epsilon RI) is a multisubunit complex comprised of either alpha gamma (2) or alpha beta gamma (2) chains. The cotranslational assembly of the IgE-binding alpha -chain with a dimer of gamma -chains occurs in a highly controlled manner and is proposed to involve masking of a dilysine motif present at the cytoplasmic C terminus of the Fc epsilon RI alpha -chain that targets localization of this subunit to the endoplasmic reticulum (ER), Here, we show that ER quality control modulates export from the ER of newly synthesized alpha gamma (2) and alpha beta gamma (2) receptors, We demonstrate that the presence of untrimmed N-linked core glycans (Gle(3)Man(9)GleNAc(2)) on the FceRI alpha -chain activates the ER quality control mechanism to retain this subunit in the ER, despite the presence of gamma -chains, At the same time, the untrimmed, ER-localized alpha -chain exhibits IgE-binding activity, suggesting that Fc epsilon RI alpha -chain folding occurs before constitutive glucose trimming. In additional experiments, we demonstrate that cell surface expression of an alpha -chain C-terminal truncation mutant is also dependent on glucose trimming, but not on gamma -chain coexpression. We suggest that glucosidase trimming of terminal glucose residues is a critical control step in the export of Fc epsilon RI alpha from the ER. Finally, we show that the constitutive ER FceRI alpha -chain, expressed in the absence of the other FceRI subunits, associates with the ER lectin-like chaperone calnexin, but not the structurally similar ER chaperone calreticulin, presumably through interaction with monoglucosylated alpha -chain ER glycoforms.