Fritzsche Susanne, Abualrous Esam T, Borchert Britta, Momburg Frank, Springer Sebastian
Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany.
Department of Translational Immunology, German Cancer Research Center/NCT, Heidelberg, Germany.
Traffic. 2015 Jun;16(6):591-603. doi: 10.1111/tra.12279. Epub 2015 Apr 16.
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-2D(b) and H-2K(b) . 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.
分泌蛋白从内质网（ER）到质膜的顺向转运是一个多步骤过程。分泌蛋白向细胞表面的转运速率差异很大，但每个步骤对这种差异的贡献却知之甚少。转运速率可能由蛋白质折叠、内质网中的伴侣蛋白结合、进入内质网出口位点（ERES）以及从内质网-高尔基体中间腔室或顺面高尔基体向内质网的回收决定。我们结合使用了折叠和运输分析方法，来确定小鼠主要组织相容性复合体（MHC）I类肽受体的两种天然同种异型H-2D(b)和H-2K(b)在细胞表面运输中的差异步骤。我们发现，一种作用于MHC I类分子折叠的腔内部分并极大地限制其进入ERES的新型内质网出口前过程，解释了这两种同种异型的运输差异。我们的观察结果支持这样一种模型，即MHC I类分子和其他I型跨膜蛋白的细胞表面运输受其所有折叠和成熟状态对内质网基质蛋白亲和力的控制。
