Redundant and Antagonistic Roles of XTP3B and OS9 in Decoding Glycan and Non-glycan Degrons in ER-Associated Degradation.
Redundant and Antagonistic Roles of XTP3B and OS9 in Decoding Glycan and Non-glycan Degrons in ER-Associated Degradation.
复制标题
XTP3B 和 OS9 在解码 ER 相关降解中的聚糖和非聚糖降解决定子中的冗余和拮抗作用。
DOI：
10.1016/j.molcel.2018.03.026
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发表时间：
2018
期刊：
影响因子：
16
通讯作者：
Kopito,RonR
中科院分区：
文献类型：
--
作者：
vanderGoot,AnnemiekeT;Pearce,MargaretMP;Leto,DaraE;Shaler,ThomasA;Kopito,RonR
在ER中参与非生产性折叠的糖蛋白被标记为通过由ER凝集素解码的底物N-聚糖的进行性去甘露糖基化产生的信号降解，但是两种凝集素OS 9和XTP 3B如何有助于非糖基化蛋白分类尚不清楚。我们产生了两种凝集素单独和组合纯合缺失的细胞系。我们发现OS 9和XTP 3B冗余地促进糖蛋白降解并稳定SEL 1 L/HRD 1错位复合物，XTP 3B深刻地抑制非糖基化蛋白的降解，OS 9拮抗这种抑制。OS 9和XTP 3B的相对表达以及同一蛋白质内聚糖和非聚糖降解决定子的分布有助于糖蛋白分类的保真度和持续合成能力，因此决定了早期分泌途径中新合成蛋白质的命运。
Glycoproteins engaged in unproductive folding in the ER are marked for degradation by a signal generated by progressive demannosylation of substrate N-glycans that is decoded by ER lectins, but how the two lectins, OS9 and XTP3B, contribute to non-glycosylated protein triage is unknown. We generated cell lines with homozygous deletions of both lectins individually and in combination. We found that OS9 and XTP3B redundantly promote glycoprotein degradation and stabilize the SEL1L/HRD1 dislocon complex, that XTP3B profoundly inhibits the degradation of non-glycosylated proteins, and that OS9 antagonizes this inhibition. The relative expression of OS9 and XTP3B and the distribution of glycan and non-glycan degrons within the same protein contribute to the fidelity and processivity of glycoprotein triage and, therefore, determine the fates of newly synthesized proteins in the early secretory pathway.