Maintaining the factory: the roles of the unfolded protein response in cellular homeostasis in plants

Abstract

Much like a factory, the endoplasmic reticulum (ER) assembles simple cellular building blocks into complex molecular machines known as proteins. In order to protect the delicate protein folding process and ensure the proper cellular delivery of protein products under environmental stresses, eukaryotes have evolved a set of signaling mechanisms known as the unfolded protein response (UPR) to increase the folding capacity of the ER. This process is particularly important in plants, because their sessile nature commands adaptation for survival rather than escape from stress. As such, plants make special use of the UPR, and evidence indicates that the master regulators and downstream effectors of the UPR have distinct roles in mediating cellular processes that affect organism growth and development as well as stress responses. In this review we outline recent developments in this field that support a strong relevance of the UPR to many areas of plant life.

Keywords: Arabidopsis thaliana; ER stress; IRE1; bZIP28; bZIP60; unfolded protein response.

Figure 1. Mechanisms of the plant UPR activation

Environmental stresses (e.g. heat, oxidative stress, selenium, chemical inhibitors) negatively affect the protein folding process, leading to the buildup of unfolded proteins. Plastid stress promotes the buildup of MEcPP (2-C-Methyl-D-erythritol-2,4-cyclopyrophosphate), which through an unknown mechanism, activates CAMTA3 (Calmodulin biding transcriptional activator 3) inducing transcription of bZIP60. 2. BiP ER luminal proteins bind unfolded proteins. The buildup of unfolded proteins leads to activation of IRE1 mediated splicing of bZIP60, which is then potentially ligated by the RNA ligase RLG1. The spliced bZIP60 is a nuclear localized transcription factor which binds to promoters of downstream UPR target genes, Regulated IRE1 dependent decay (RIDD) although not depicted here, regulates mRNA abundance and it is active during ER stress. 3. bZIP28 after being freed from BiPs by the presence of unfolded proteins is trafficked to the Golgi in a SAR1a/SEC23-dependent way. S2P proteases cleave the active transcription factor from its transmembrane domain. bZIP28 enters the nucleus and acts redundantly with bZIP60 to transcriptionally activate the UPR.

Figure 2. UPR-regulated Transcription Factors may Tailor UPR Activation to Specific Stress Combinations

Several plant-specific transcription factors are upregulated under ER stress in an IRE1/bZIP28 dependent way. Two membrane-bound transcription factors, ANAC062 and ANAC089, have been shown to relocate to the nucleus under ER stress. ANAC062 also is nuclear localized under cold stress conditions. ANAC089 along with interactor PAS1 (PASTICCINO1) were also shown to relocate to the nucleus in roots treated with 1-naphthaleneacetic acid to induce dedifferentiation. ANAC103, a soluble transcription factor, was also shown to upregulate UPR genes upon over expression. Although truncated forms of these transcription factors were shown to upregulate UPR responsive genes, the molecular mechanisms of action of native transcription factors are still unknown. After upregulation by IRE1/bZIP28 dependent mechanisms, these transcription factors may respond to secondary signals which reinforce or alter UPR gene expression.