A plasma membrane-tethered transcription factor, NAC062/ANAC062/NTL6, mediates the unfolded protein response in Arabidopsis
A plasma membrane-tethered transcription factor, NAC062/ANAC062/NTL6, mediates the unfolded protein response in Arabidopsis
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拟南芥中质膜束缚的转录因子 NAC062/ANAC062/NTL6 介导未折叠蛋白反应。
DOI：
10.1111/tpj.12604
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发表时间：
2014-09-01
期刊：
影响因子：
7.2
通讯作者：
Liu, Jian-Xiang
中科院分区：
文献类型：
--
作者：
Yang, Zheng-Ting;Lu, Sun-Jie;Liu, Jian-Xiang
在真核细胞中，未折叠或错误折叠的蛋白质在内质网(ER)中积累，触发了一种被称为未折叠蛋白反应(UPR)的保守途径，以减轻内质网应激。S2P-bZIP28和IRE1-bZIP60两条信号通路在将ER胁迫信号从内质网传递到细胞核中起着重要作用。目前尚不清楚分泌途径中的其他成分是否也有助于缓解内质网应激。在这里，我们报道了一个质膜相关的转录因子NAC062(也称为ANAC062/NTL6)，它是拟南芥中另一个重要的UPR介体。NAC062在拟南芥中定位于细胞膜，并调控ER逆境反应基因的表达。野生型背景中NAC062的敲除增加了内质网应激敏感性，而核定位形式的NAC062D在bZIP28和bZIP60双突变体(Zip28zip60)背景中的诱导表达提高了内质网应激耐受性。在正常生长条件下，NAC062基因的敲除减弱了ER应激诱导的UPR下游基因的表达，而NAC062D-MYC的过表达则诱导了UPR下游基因的表达。芯片定量聚合酶链式反应显示，NAC062D-MYC富含在几个UPR下游基因的启动子区域，如BiP2。此外，NAC062本身也受到内质网胁迫的上调，内质网胁迫依赖于bZIP60而不是bZIP28。因此，我们的结果在植物中发现了另一条UPR途径，在该途径中，膜相关转录因子NAC062将ER胁迫信号从质膜传递到细胞核，并在调节UPR下游基因表达方面发挥重要作用。
The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) triggers a well conserved pathway called the unfolded protein response (UPR) in eukaryotic cells to mitigate ER stress. Two signaling pathways, S2P-bZIP28 and IRE1-bZIP60, play important roles in transmitting ER stress signals from the ER to the nucleus in Arabidopsis (Arabidopsis thaliana). It is not known whether other components in the secretory pathway also contribute to the alleviation of ER stress. Here we report the identification of a plasma membrane-associated transcription factor, NAC062 (also known as ANAC062/NTL6), as another important UPR mediator in Arabidopsis plants. NAC062 relocates from the plasma membrane to the nucleus and regulates the expression of ER stress responsive genes in Arabidopsis. Knock-down of NAC062 in the wild-type background confers ER stress sensitivity, while inducible expression of a nucleus-localized form of NAC062, NAC062D, in the bZIP28 and bZIP60 double mutant (zip28zip60) background increases ER stress tolerance. Knock-down of NAC062 impairs ER-stress-induced expression of UPR downstream genes while over-expression of NAC062D-MYC induces the expression of UPR downstream genes under normal growth condition. CHIP-qPCR reveals that NAC062D-MYC is enriched at the promoter regions of several UPR downstream genes such as BiP2. Furthermore, NAC062 itself is also up-regulated by ER stress, which is dependent on bZIP60 but not on bZIP28. Thus, our results have uncovered an alternative UPR pathway in plants in which the membrane-associated transcription factor NAC062 relays ER stress signaling from the plasma membrane to the nucleus and plays important roles in regulating UPR downstream gene expression.