Functional Diversification of ER Stress Responses in Arabidopsis

Abstract

The endoplasmic reticulum (ER) is responsible for the synthesis of one-third of the cellular proteome and is constantly challenged by physiological and environmental situations that can perturb its homeostasis and lead to the accumulation of misfolded secretory proteins, a condition referred to as ER stress. In response, the ER evokes a set of intracellular signaling processes, collectively known as the unfolded protein response (UPR), which are designed to restore biosynthetic capacity of the ER. As single-cell organisms evolved into multicellular life, the UPR complexity has increased to suit their growth and development. In this review, we discuss recent advances in the understanding of the UPR, emphasizing conserved UPR elements between plants and metazoans and highlighting unique plant-specific features.

Keywords: Arabidopsis thaliana.; ER stress; unfolded protein response (UPR).

Figure 1.. Mechanisms of activation of the ER stress sensors in plants

(A) In plants, IRE1A and IRE1B have a luminal domain and cytosolic kinase and RNase domains. By similarity with yeast and metazoans, it has been proposed that the interaction between BiP and the luminal domain of IRE1 may keep the lattes in an inactive monomeric state. Upon the accumulation of unfolded proteins, BIP dissociates from IRE1, leading to IRE1 homodimerization and auto-transphosphorylation as well as promoting activation of the RNase domain. In plants, the RNase domain catalyzes two processes: the unconventional splicing of bZIP60 mRNA producing the translation of an active TF, bZIP60 (pathway 1), and the selective degradation of mRNAs (RIDD) (pathway 2), which has been associated with autophagy. If the IRE1-kinase domain phosphorylates other functional substrates besides itself has not been yet establish (pathway 3). The recent identification of IRE1C (pathway 4), which lacks the luminal domain, raises questions about its mechanism of activation and its functional implication in the response to stressors (Outstanding questions). (B) The activation of bZIP28 is mediated by its interaction with BiP (pathway 1). An accumulation of unfolded proteins causes the dissociation of BiP from the bZIP28 luminal domain leading to its Golgi translocation. Once in the Golgi, bZIP28 is cleaved first by unknown protease(s), possibly by S1P, and then by S2P. This process releases the active TF from the membrane anchor for nuclear translocation. Although the activation mechanism of bZIP17 may be similar to bZIP28 (pathway 2), the interacting proteins that retain bZIP17 in the ER under normal conditions has not been described yet. CT, cytoplasm; LM, ER lumen; N, nucleus.

Figure 2.. Nuclear regulation of the UPR TFs binding to cis-elements in the plants.

In the nucleus, the active forms of bZIP28 and bZIP60 bind to the cis-elements responsive to ER stress (e.g. ER Stress responsible Element-1, ERSE-I and Unfolded Protein Response Element-1, UPRE-I). Their transcriptional activity is enhanced (blue dotted lines) or inhibited (red dotted lines) by interactioning with other transcription regulators associated with other biological pathways. The COMPASS-like complex increases the levels of H3K4me3 in the promoters of UPR target genes, causing gene expression modulation. CP, chloroplast; ER; endoplasmic reticulum; G, Golgi; MT, mitochondria; VC, vacuole; ER, endoplasmic reticulum.

Figure 3.. Mechanisms for the systemic signaling of UPR in the whole plant.

Abiotic (such as heat, salt or light) and biotic (pathogen attack) stresses in combination with physiological processes can elicit the UPR activation. For the whole plant adaptation, plants can evoke a long-distance signaling to communicate the occurrence of ER stress in a tissue to other tissue a systemic by the ROS molecules produced during the ER stress response and also by the cell-to-cell translocation of active bZIP60 TF and the spliced bZIP60 mRNA (sBZIP60) through the plasmodesmata.