Allele-specific suppression of a defective brassinosteroid receptor reveals a physiological role of UGGT in ER quality control
Allele-specific suppression of a defective brassinosteroid receptor reveals a physiological role of UGGT in ER quality control
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DOI：
10.1016/j.molcel.2007.05.015
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发表时间：
2007-06-22
期刊：
影响因子：
16
通讯作者：
Li, Jianming
中科院分区：
文献类型：
--
作者：
Jin, Hua;Yan, Zhenyan;Li, Jianming
UDP-葡萄糖：糖蛋白葡萄糖基转移酶（UGGT）被认为是内质网（ER）中蛋白质质量控制的折叠传感器。以前的非生理底物的生化研究表明，UGGT可以通过识别细微的折叠缺陷使非天然糖蛋白糖基化;然而，其生理功能仍然不确定。在这里，我们表明，突变拟南芥EBS 1基因抑制生长缺陷的油菜素类固醇（BR）受体突变体，bri 1 -9，在等位基因特异性的方式恢复其1313的敏感性。利用图位克隆策略，我们发现EBS 1编码拟南芥UGGT同源物。我们证明了bri 1 -9通过与几种ER分子伴侣的相互作用保留在ER中，并且ebs 1突变显著降低了基于保留的ER质量控制的严格性，允许将结构不完善但生物化学活性的bri 1 -9出口到细胞表面用于BR感知。因此，我们的发现为UGGT在高保真ER质量控制中的生理作用提供了遗传支持。
UDP-glucose:glycoprotein glucosyltransferase (UGGT) is a presumed folding sensor of protein quality control in the endoplasmic reticulum (ER). Previous biochemical studies with non-physiological substrates revealed that UGGT can glucosylate nonnative glycoproteins by recognizing subtle folding defects; however, its physiological function remains undefined. Here, we show that mutations in the Arabidopsis EBS1 gene suppressed the growth defects of a brassinosteroid (BR) receptor mutant, bri1-9, in an allele-specific manner by restoring its 1313 sensitivity. Using a map-based cloning strategy, we discovered that EBS1 encodes the Arabidopsis homolog of UGGT. We demonstrated that bri1-9 is retained in the ER through interactions with several ER chaperones and that ebs1 mutations significantly reduce the stringency of the retention-based ER quality control, allowing export of the structurally imperfect yet biochemically competent bri1-9 to the cell surface for BR perception. Thus, our discovery provides genetic support for a physiological role of UGGT in high-fidelity ER quality control.