Letourneur F, Hennecke S, Démollière C, Cosson P
Basel Institute for Immunology, Switzerland.
J Cell Biol. 1995 May;129(4):971-8. doi: 10.1083/jcb.129.4.971.
Signals that can cause retention in the ER have been found in the cytoplasmic domain of individual subunits of multimeric receptors destined to the cell surface. To study how ER retention motifs are masked during assembly of oligomeric receptors, we analyzed the assembly and intracellular transport of the human high-affinity receptor for immunoglobulin E expressed in COS cells. The cytoplasmic domain of the alpha chain contains a dilysine ER retention signal, which becomes nonfunctional after assembly with the gamma chain, allowing transport out of the ER of the fully assembled receptor. Juxtaposition of the cytoplasmic domains of the alpha and gamma subunits during assembly is responsible for this loss of ER retention. Substitution of the gamma chain cytoplasmic domain with cytoplasmic domains of irrelevant proteins resulted in efficient transport out of the ER of the alpha chain, demonstrating that nonspecific steric hindrance by the cytoplasmic domain of the gamma chain accounts for the masking of the ER retention signal present in the cytoplasmic domain of the alpha chain. Such a mechanism allows the ER retention machinery to discriminate between assembled and nonassembled receptors, and thus participates in quality control at the level of the ER.
在注定要到达细胞表面的多聚体受体的各个亚基的胞质结构域中，已发现可导致在内质网中滞留的信号。为了研究内质网滞留基序在寡聚体受体组装过程中是如何被掩盖的，我们分析了在COS细胞中表达的人免疫球蛋白E高亲和力受体的组装和细胞内运输。α链的胞质结构域包含一个双赖氨酸内质网滞留信号，在与γ链组装后该信号失去功能，从而使完全组装好的受体能够运输出内质网。组装过程中α和γ亚基的胞质结构域并列导致了这种内质网滞留功能的丧失。用无关蛋白质的胞质结构域替换γ链胞质结构域，导致α链有效地运输出内质网，这表明γ链胞质结构域的非特异性空间位阻导致了α链胞质结构域中存在的内质网滞留信号被掩盖。这种机制使内质网滞留机制能够区分组装好的受体和未组装的受体，从而参与内质网水平的质量控制。
