Abstract
Stress caused by environmental conditions or physiological growth can lead to an accumulation of unfolded proteins in the endoplasmic reticulum (ER) causing ER stress, which in turn triggers a cytoprotective mechanism termed the unfolded protein response (UPR). Under mild-short stress conditions the UPR can restore ER functioning and cell growth, such as reducing the load of unfolded proteins through the upregulation of genes involved in protein folding and in degrading mis-folded proteins, and through autophagy activation, but it can also lead to cell death under prolonged and severe stress conditions. A diversified suite of sensors has been evolved in the eukaryotic lineages to orchestrate the UPR most likely to suit the cell’s necessity to respond to the different kinds of stress in a conserved as well as species-specific manner. In plants three UPR sensors cooperate with non-identical signaling pathways: the protein kinase inositol-requiring enzyme (IRE1), the ER-membrane-associated transcription factor bZIP28, and the GTP-binding protein β1 (AGB1). In this mini-review, we show how plants differ from the better characterized metazoans and fungi, providing an overview of the signaling pathways of the UPR, and highlighting the overlapping and the peculiar roles of the different UPR branches in light of evolutionary divergences in eukaryotic kingdoms.
Highlights
Environmental or physiological conditions that interfere with the proper protein folding in the endoplasmic reticulum (ER) lead to an accumulation of potentially toxic mis-folded proteins, a condition generally termed as “ER stress”
This review focuses on the current understanding of how the unfolded protein response (UPR) signaling pathways initiate and progress in response to the severity and duration of ER stress and addresses the overlapping and unique roles of the UPR response in eukaryotes with emphasis on multicellular eukaryotes
UPR ARMS IN EUKARYOTES AND THEIR ER STRESS-SENSING MECHANISMS In the yeast Saccharomyces cerevisiae, the UPR is mediated by inositol-requiring enzyme1 (IRE1; Ire1p; Cox et al, 1993; Mori et al, 1993), an ER-resident protein largely conserved in eukaryotes
Summary
Environmental or physiological conditions that interfere with the proper protein folding in the endoplasmic reticulum (ER) lead to an accumulation of potentially toxic mis-folded proteins, a condition generally termed as “ER stress”. To restore ER homeostasis, a network of inter-organelle signaling pathways mediates the “unfolded protein response” (UPR), leading to an increase of protein folding capacity in the ER (Walter and Ron, 2011). If these mechanisms of adaptation and survival to ER stress fail, the UPR signaling leads the cells toward cell death (Hetz, 2012). ATF6 is a type II transmembrane protein, characterized by a C-terminal ER lumen domain and an N-terminal cytosolic domain containing a bZIP (basic leucine zipper) transcriptional factor domain, while PERK is a type I transmembrane protein, with an ER-luminal stress-sensing domain and a cytosolic Ser/Thr kinase domain (Figure 1A). The mechanisms of how ER stress is sensed have been partially defined: the UPR sensors may detect ER stress (1) through the dissociation of their ER-luminal stress-sensing domain from the ER chaperones, which would be induced by the binding of ER chaperones to unfolded proteins, as shown for IRE1α, PERK, and ATF6 in metazoans (Kimata and Kohno, 2011); (2) through the direct binding of the ER-luminal domain of the UPR sensors to the www.frontiersin.org
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