Garstka Malgorzata, Borchert Britta, Al-Balushi Mohammed, Praveen P V K, Kühl Nicole, Majoul Irina, Duden Rainer, Springer Sebastian
Biochemistry and Cell Biology, School of Engineering and Science, Jacobs University Bremen, 28759 Bremen, Germany.
J Biol Chem. 2007 Oct 19;282(42):30680-90. doi: 10.1074/jbc.M701721200. Epub 2007 Jul 26.
Prior to binding to a high affinity peptide and transporting it to the cell surface, major histocompatibility complex class I molecules are retained inside the cell by retention in the endoplasmic reticulum (ER), recycling through the ER-Golgi intermediate compartment and possibly the cis-Golgi, or both. Using fluorescence microscopy and a novel in vitro COPII (ER-to-ER-Golgi intermediate compartment) vesicle formation assay, we find that in both lymphocytes and fibroblasts that lack the functional transporter associated with antigen presentation, class I molecules exit the ER and reach the cis-Golgi. Intriguingly, in wild-type T1 lymphoma cells, peptide-occupied and peptide-receptive class I molecules are simultaneously exported from ER membranes with similar efficiencies. Our results suggest that binding of high affinity peptide and exit from the ER are not coupled, that the major histocompatibility complex class I quality control compartment extends into the Golgi apparatus under standard conditions, and that peptide loading onto class I molecules may occur in post-ER compartments.
在与高亲和力肽结合并将其转运到细胞表面之前，主要组织相容性复合体I类分子通过在内质网（ER）中滞留、通过ER-高尔基体中间腔室以及可能的顺面高尔基体循环或两者兼而有之而被保留在细胞内。使用荧光显微镜和一种新型的体外COPII（从ER到ER-高尔基体中间腔室）囊泡形成试验，我们发现在缺乏与抗原呈递相关的功能性转运体的淋巴细胞和成纤维细胞中，I类分子都能离开ER并到达顺面高尔基体。有趣的是，在野生型T1淋巴瘤细胞中，肽占据的和肽接受性的I类分子同时以相似的效率从ER膜中输出。我们的结果表明，高亲和力肽的结合与从ER中输出并不耦合，主要组织相容性复合体I类质量控制区室在标准条件下延伸到高尔基体中，并且I类分子上的肽加载可能发生在ER后的区室中。
