Release from Endoplasmic Reticulum Matrix Proteins Controls Cell Surface Transport of MHC Class I Molecules
Release from Endoplasmic Reticulum Matrix Proteins Controls Cell Surface Transport of MHC Class I Molecules
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DOI：
10.1111/tra.12279
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发表时间：
2015-06
期刊：
影响因子：
4.5
通讯作者：
Susanne Fritzsche;Esam T. Abualrous;Britta Borchert;F. Momburg;S. Springer
中科院分区：
文献类型：
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作者：
Susanne Fritzsche;Esam T. Abualrous;Britta Borchert;F. Momburg;S. Springer
分泌蛋白从内质网到质膜的顺行运输是一个多步骤的过程。分泌蛋白在运输到细胞表面的速率上有很大的不同，但每一步对这种差异的贡献却知之甚少。转运速率可由蛋白质折叠、内质网中的伴侣结合、进入内质网出口部位(ERES)以及从内质网高尔基体中间区或顺式高尔基体到内质网的取回来决定。我们使用折叠和转运试验相结合的方法来鉴定小鼠主要组织相容性复合体(MHC)I类多肽受体的两个自然同种异型H-2db和H-2kb在细胞表面运输中的差异步骤。我们发现，作用于MHC I类分子折叠的管腔部分并极大地限制了它们对ERES的访问的一种新颖的ER前退出过程解释了这两种同种异型的运输差异。我们的观察支持这样一个模型，即MHC I类分子和其他I类跨膜蛋白的细胞表面运输由它们所有的折叠和成熟状态与内质网基质蛋白的亲和力决定。
The anterograde transport of secretory proteins from the endoplasmic reticulum (ER) to the plasma membrane is a multi‐step process. Secretory proteins differ greatly in their transport rates to the cell surface, but the contribution of each individual step to this difference is poorly understood. Transport rates may be determined by protein folding, chaperone association in the ER, access to ER exit sites (ERES) and retrieval from the ER‐Golgi intermediate compartment or the cis‐Golgi to the ER. We have used a combination of folding and trafficking assays to identify the differential step in the cell surface transport of two natural allotypes of the murine major histocompatibility complex (MHC) class I peptide receptor, H‐2Db and H‐2Kb. We find that a novel pre‐ER exit process that acts on the folded lumenal part of MHC class I molecules and that drastically limits their access to ERES accounts for the transport difference of the two allotypes. Our observations support a model in which the cell surface transport of MHC class I molecules and other type I transmembrane proteins is governed by the affinity of all their folding and maturation states to the proteins of the ER matrix.