Endoplasmic Reticulum Stress Sensing in the Unfolded Protein Response
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TLDR
The mechanistic principles of ER stress sensing are the focus of this review, and yeast Ire1 directly binds to unfolded proteins, which induces its oligomerization and activation.Abstract:
Secretory and transmembrane proteins enter the endoplasmic reticulum (ER) as unfolded proteins and exit as either folded proteins in transit to their target organelles or as misfolded proteins targeted for degradation. The unfolded protein response (UPR) maintains the protein-folding homeostasis within the ER, ensuring that the protein-folding capacity of the ER meets the load of client proteins. Activation of the UPR depends on three ER stress sensor proteins, Ire1, PERK, and ATF6. Although the consequences of activation are well understood, how these sensors detect ER stress remains unclear. Recent evidence suggests that yeast Ire1 directly binds to unfolded proteins, which induces its oligomerization and activation. BiP dissociation from Ire1 regulates this oligomeric equilibrium, ultimately modulating Ire1’s sensitivity and duration of activation. The mechanistic principles of ER stress sensing are the focus of this review.read more
Citations
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Endoplasmic reticulum stress in sepsis
TL;DR: Current research in the context of ER stress and UPR signaling associated with sepsis and its related clinical conditions, such as trauma-hemorrhage and ischemia/reperfusion injury are summarized.
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Unfolded Protein Response-regulated Drosophila Fic (dFic) Protein Reversibly AMPylates BiP Chaperone during Endoplasmic Reticulum Homeostasis
TL;DR: The inactive conformation of BiP is the preferred substrate for dFic, thus endorsing a model whereby AMPylation regulates the function of BiFic as a chaperone, allowing acute activation ofBiP by deAMPylation during an ER stress response.
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Compromised Mitochondrial Protein Import Acts as a Signal for UPRmt.
Stéphane G. Rolland,Sandra Schneid,Melanie Schwarz,Elisabeth Rackles,Christian Fischer,Simon Haeussler,Saroj G. Regmi,Assa Yeroslaviz,Bianca Habermann,Dejana Mokranjac,Eric J. Lambie,Barbara Conradt,Barbara Conradt +12 more
TL;DR: It is proposed that compromised mitochondrial protein import signals the induction of UPRmt and that the mitochondrial targeting sequence of ATFS-1 functions as a sensor for this signal.
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Ceapins inhibit ATF6α signaling by selectively preventing transport of ATF6α to the Golgi apparatus during ER stress.
Ciara M Gallagher,Peter Walter +1 more
TL;DR: In this paper, the authors investigated the role of small molecules in preventing the protein from moving to the Golgi apparatus by keeping it away from the machinery that moves proteins between these compartments, and found that small clusters of ATF6α in unstressed cells act to keep this protein in the endoplasmic reticulum.
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NMDA Receptors Are Upregulated and Trafficked to the Plasma Membrane after Sigma-1 Receptor Activation in the Rat Hippocampus
Mohan Pabba,Adrian Y. C. Wong,Nina Ahlskog,Elitza Hristova,Dante Biscaro,Wissam Nassrallah,Johnny K. Ngsee,Melissa A. Snyder,Jean-Claude Béïque,Richard Bergeron +9 more
TL;DR: It is demonstrated that in vivo administration of the selective σ-1R agonists increases the expression of GluN2A and GLUN2B subunits, as well as postsynaptic density protein 95 in the rat hippocampus and mediates trafficking of NMDARs to the cell surface, suggesting that �oR may play an important role in N MDAR-mediated functions, such as learning and memory.
References
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Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus.
Caroline E. Shamu,Peter Walter +1 more
TL;DR: Molecular genetic and biochemical studies described here suggest that, as in the case of growth factor receptors of higher eukaryotic cells, Ire1p oligomerizes in response to the accumulation of unfolded proteins in the ER and is phosphorylated in trans by otherIre1p molecules as a result of oligomerization.
Journal ArticleDOI
The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation
Peter Walter,David Ron +1 more
TL;DR: The vast majority of proteins that a cell secretes or displays on its surface first enter the endoplasmic reticulum, where they fold and assemble, and only properly assembled proteins advance from the ER to the cell surface.
Journal ArticleDOI
XBP1 mRNA Is Induced by ATF6 and Spliced by IRE1 in Response to ER Stress to Produce a Highly Active Transcription Factor
TL;DR: The transcription factor XBP1, a target of ATF6, is identified as a mammalian substrate of such an unconventional mRNA splicing system and it is shown that only the spliced form of X BP1 can activate the UPR efficiently.
Journal ArticleDOI
Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase
TL;DR: The cloning of perk is described, a gene encoding a type I transmembrane ER-resident protein that contains a protein-kinase domain most similar to that of the known eIF2α kinases, PKR and HRI that implicate PERK in a signalling pathway that attenuates protein translation in response to ER stress.
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