2018 Feb 20
Activation of the Transducers of Unfolded Protein Response in Plants
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Activation of the Transducers of Unfolded Protein Response in Plants
Front Plant Sci
Maintenance of homeostasis of the endoplasmic reticulum (ER) ensures the balance between loading of nascent proteins and their secretion. Certain developmental conditions or environmental stressors affect protein folding causing ER stress. The resultant ER stress is mitigated by upregulating a set of stress-responsive genes in the nucleus modulating the mechanism of the unfolded protein response (UPR). In plants, the UPR is mediated by two major pathways; by the proteolytic processing of bZIP17/28 and by the IRE1-mediated splicing of
bZIP60 mRNA. Recent studies have shown the involvement of plant-specific NAC transcription factors in UPR regulation. The molecular mechanisms activating plant-UPR transducers are only recently being unveiled. This review focuses on important structural features involved in the activation of the UPR transducers like bZIP17/28/60, IRE1, BAG7, and NAC017/062/089/103. Also, we discuss the activation of the UPR pathways, including BAG7-bZIP28 and IRE1-bZIP60, in detail, together with the NAC-TFs, which adds a new paradigm to the plant UPR.
IRE1; NAC-TFs; UPR activation; abiotic/biotic stress; bZIP28; bZIP60; endoplasmic reticulum.
Activation of the unfolded protein response (UPR) in Arabidopsis in response to external stresses. Abiotic (high light intensity, temperature, salt, drought, and heavy metals) and biotic (pathogenic attack) stresses disturb protein folding in the ER lumen causing the activation of transcription factors (TFs), which bind to the ER stress response elements (ERSEs) to upregulate the UPR genes. The UPR plays an important role during vegetative root growth and reproductive development in Arabidopsis. Moreover, plant signaling compounds such as 2-C-methyl-
D-erythritol-2,4-cyclopyrophosphate (MEcPP) and salicylic acid (SA) activate the UPR pathways via unknown mechanisms.
Schematic representation of the structural features of the signal transducers of the unfolded protein response (UPR) in Arabidopsis. The molecular structures of the Arabidopsis signal transducing elements in the UPR pathway are schematically represented. The structural features of the bZIP/NAC-TFs, coregulators-BAG7, and dual-functioning enzymes-IRE1 are briefly depicted.
ER stress induced activation of bZIP28 and BAG7 in plant UPR signaling. Under normal conditions, the bZIP28 and BAG7 proteins are anchored to the ER membrane by interactions with the Binding protein (BiP). However, in response to ER stress, BiP assists the proper folding of the unfolded proteins. Then the released bZIP28 traffics to the Golgi through the Coat Protein II (COPII) vesicles. After the proteolytic cleaving of the bZIP28 by an unknown protease (X?) and by the site-2 protease (S2P), the truncated active form of bZIP28 translocates into the nucleus. The nuclear bZIP28 outcompetes HY5 for binding to the ERSE element and forms a transcriptional complex with bZIP60 and NF-Y-TFs to activate the UPR gene expression. The 26S-proteasomal degradation system eventually degrades the released HY5. Additionally, BAG7 is also released from the ER membrane by an unknown protease (X?). Subsequently, BAG7 is sumoylated and enters the nucleus. The nuclear BAG7 interacts with WRKY29 and regulates the expression of BAG7 and other chaperone proteins to mitigate ER stress.
Activation of the IRE1-bZIP60 mediated UPR pathway against ER stress. Under normal conditions, the sensor domain of IRE1 binds to the ER-luminal Binding protein (BiP) and the full-length bZIP60 is anchored in the ER membrane. In response to ER-stress, 2-C-methyl-
D-erythritol-2,4-cyclopyrophosphate (MEcPP) is accumulated in the chloroplast and activates the Calmodulin-Binding Transcription Activator 3 (CAMTA3)-TF, which binds to the rapid stress response element (RSRE) and up-regulates bZIP60 expression. A1–A6 indicates the step-wise activation process of IRE1. (A1) In response to ER stress, BiP dissociates from IRE1 to assist the proper folding of the accumulated unfolded proteins. The released IRE1 is dimerized to align its cytosolic kinase domains in such a way that they trans-autophosphorylate each other to activate the RNase function. (A2) The luminal domain of IRE1 binds to the hydrophobic domain of the unfolded proteins and triggers oligomerization and clustering. (A3) The mRNAs encoding the secretory pathway proteins are promiscuously cleaved by the proteins of the regulated IRE1-dependent decay (RIDD) pathway. (A4) The basic linker region of IRE1 mediates specific recruitment and docking of the unspliced bZIP60 mRNA to IRE1 clusters where it is cleaved explicitly at the two conserved sites (CXG| XXG) present in the kissing stem–loop structure. (A5) The tRNA ligase RLG1 catalyzes the ligation of the resulting fragments of the bZIP60 mRNA. (A6) Translation of the spliced bZIP60 mRNA results in the production of the active bZIP60 protein (bZIP60s). It translocates to the nucleus forming the bZIP28-NF-Y-TFs complex. These TF-complexes bind to the ERSE element of the UPR genes and positively regulate the UPR-related downstream gene expression.
Activation of the NAC-TFs mediated UPR signaling pathways in response to ER stress. In response to ER stress, bZIP60s binds to the UPR element-II/III (UPRE-II/III) to transcriptionally upregulate the expression of NAC062 and NAC103. An unknown protease activates the plasma membrane-localized NAC062. A rhomboid protease is involved in the activation of the ER membrane-localized NAC017. The nuclear localized-NAC103 along with the activated NAC017/062 binds to the NAC-binding sites and activates the UPR gene expressions. Under chronic ER stress conditions, bZIP28/60s binds to the UPRE-I element of the
NAC089 promoter and activates its gene expression. Moreover, NAC089 is processed by an unknown protease and translocates to the nucleus to upregulate the genes involved in programmed cell death (PCD).
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