Endoplasmic reticulum chaperone gp96 is required for innate immunity but not cell viability
Endoplasmic reticulum chaperone gp96 is required for innate immunity but not cell viability
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DOI：
10.1038/ncb1001-891
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发表时间：
2001-10-01
影响因子：
21.3
通讯作者：
Seed, B
中科院分区：
文献类型：
--
作者：
Randow, F;Seed, B
伴侣蛋白被认为可以促进新合成蛋白质的正确折叠和组装，并有助于在有利于蛋白质变性的环境条件下恢复折叠状态。它们是所有蛋白质中最普遍且高度保守的蛋白质之一。长期以来，人们一直认为真核内质网 (ER) 伴侣 gp96 对于细胞生存是不可或缺的。在这里，我们报告说，对细菌内毒素免疫反应所需基因的筛选发现了一种缺乏 gp96 的 B 细胞系。即使在应激条件下，gp96 的缺失也能保证细胞的生存，并导致仅一小部分细胞表面受体的形成出现缺陷。在没有 gp96 的情况下，Toll 样受体保留在细胞内，这解释了突变体对微生物刺激无反应的原因。
Chaperone proteins are thought to promote the correct folding and assembly of newly synthesized proteins and to facilitate restoration of the folded state under environmental conditions that favour protein denaturation. They are among the most ubiquitous and highly conserved of all proteins. The eukaryotic endoplasmic reticulum (ER) chaperone gp96 in particular has long been thought to be indispensable for cell survival. Here we report that a screen for genes required for the immune response to bacterial endotoxins has identified a B-cell line deficient in gp96. Absence of gp96 is compatible with cellular survival even under stress conditions and causes a defect in the formation of only a small subset of cell surface receptors. Toll-like receptors are retained intracellularly in the absence of gp96, explaining the unresponsiveness of the mutant to microbial stimuli.