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STRESS BIOLOGY

Adverse environmental conditions as well as physiological situations requiring enhanced secretory protein synthesis can cause an imbalance between demand and capacity of protein synthesis at the endoplasmic reticulum (ER). The ER can sense stress and restore homeostasis by invoking a protective signaling pathway known as the unfolded protein response (UPR). To initiate UPR, yeast largely relies on a linear arm based on the action of a conserved sensor, Ire1p. During the course of evolution, the suite of UPR arms harnessed additional sensors to accommodate more specific responses in a multicellular context. A major challenge in UPR studies is now to understand the biological role of the various UPR arms in intact organisms to define how the UPR signaling network functions to direct diverse cell-fate decisions in development and response to biotic and abiotic stress. In our lab we take advantage of the conservation of plant and metazoan UPR and the availability of powerful genomics and molecular tools in the model plant Arabidopsis thaliana to address these questions. 

stress

Figure 1. Overview of unfolded protein response (UPR) arms in eukaryotes. The inositol-requiring enzyme 1 (IRE1) arm is conserved in eukaryotes. IRE1 unconventionally splices the bZIP transcription factors Xbp-1 and bZIP60 and Hac1 mRNA in mammals, plants, and yeast, respectively. The spliced bZIP transcription factor enters into the nucleus to regulate UPR target genes. In addition, two distinct arms mediated by PERK and ATF6 regulate the mammalian UPR. ATF6 is an endoplasmic reticulum (ER) transmembrane transcription factor. ER stress triggers the relocation of ATF6 from the ER to the Golgi apparatus, where it undergoes proteolytic cleavage. Subsequently, the transcription factor domain of ATF6 enters into the nucleus to modulate transcription of UPR target genes. Two functional homologs of ATF6, bZIP17, and bZIP28, exist in plants. PERK, an ER transmembrane protein kinase, is identified only in animals. On ER stress, PERK phosphorylates eukaryotic initiation factor 2 alpha (eIF2α), which leads to transient inhibition of general protein translation and selective translation of the transcription factor ATF4. Under irremediable ER stress, PERK–elF2α–ATF4–CHOP and IRE1–JNK initiate apoptosis in mammals. Moreover, the beta subunit of the heterotrimeric G protein complex AGB1 is essential for the plant UPR. Although the G protein complex is conserved in eukaryotes, its significance in the UPR is unclear in other eukaryotic organisms. Blue, eukaryotes; black, mammals; green, plants; red, yeast. (Figure from: Chen Y, Brandizzi F. IRE1: ER stress sensor and cell fate executor. Trends Cell Biol. 2013 Nov;23(11):547-55).