All transcripts were created with artificial intelligence software and modified with manual review by a third party. Although we make every effort to ensure accuracy with the manual review, some may contain computer-generated mistranslations resulting in inaccurate or nonsensical word combinations, or unintentional language. FASEB and the presenting speakers did not review the transcripts and are not responsible and will not be held liable for damages, financial or otherwise, that occur as a result of transcript inaccuracies.
New and Unexpected Connections of the Plant ER
Federica Brandizzi1,2,3
1MSU-DOE Plant Research Lab, Michigan State University, East Lansing, Michigan
2Department of Plant Biology, Michigan State University, East Lansing, Michigan
3DOE-Great Lakes Bioenergy Research Center, Michigan State University, East Lansing, Michigan
Background: Perturbations of the biosynthetic capacity of the endoplasmic reticulum (ER) due to developmental transitions or environmental stressors can cause the accumulation of misfolded proteins in the ER, a condition known as ER stress. If unmitigated, ER stress is conducive to cell death, and as such it has been recognized as a significant underlying factor in devastating human diseases and crop losses. During evolution, to mitigate ER stress, eukaryotes have developed sophisticated signaling pathways, collectively known as the unfolded protein response (UPR). As a result, in multicellular eukaryotes the UPR has acquired unique features to suit their tissue and developmental complexity and coordinate stress responses with other signaling pathways operating to maintain organ growth and prevent death.
Aims: Despite the advances on the molecular mechanisms controlling the activity of the UPR master regulators, much less is known about the mechanisms that such regulators use to control growth during stress and life-or-death decisions in intact multicellular organisms. To fill this significant knowledge gap and provide new insights into the molecular mechanisms supporting efficient UPR in intact multicellular organisms, we aimed to understand how the UPR management intersects with organ growth during stress and when stress is either resolved or unresolved.
Results: For our work, we adopted the model plant species Arabidopsis thaliana. With its genomics and genetic resources, this species allows investigating the UPR at the molecular level and gather new insights that are relevant at a whole-organism level. Using genetic encoded reporters and grafting analyses, we were able to demonstrate that the UPR constitutes a systemic signal. Furthermore, using a genomics approach, we were able to demonstrate that the transcription regulation activity of the two major bZIP-transcription factors (TFs) bZIP28 and bZIP60 during ER stress depends on their competition for the cis-regulatory element G-box of UPR gene targets with the abscisic acid-related regulator G-class bZIP TF2 (GBF2), which acts as a repressor of UPR gene expression. Then, by mining the UPR gene reprogramming roles of bZIP28 and bZIP60, we identified key genes operating downstream of these bZIP-TFs, namely COW1 and YIP1. Using reverse genetics approaches, we demonstrated a critical role of these effectors in resumption of growth upon ER stress mitigation. Finally, by carrying out a genome-wide suppressor screen of the lethality of an IRE1 loss-of-function mutant in conditions of unresolved ER stress, we were able to identify prosurvival effectors acting downstream of IRE1 in life-or-death decisions.
Conclusions: Using systems biology approaches in the model plant species Arabidopsis thaliana, we were able to identify and characterize new effectors of the UPR, which mechanistically connect ER stress management and growth at a whole organism level.
This research was funded by grant R35GM136637 from the National Institutes of Health.