Endoplasmic Reticulum Stress Sensing in the Unfolded Protein Response
Reads0
Chats0
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
More filters
Journal ArticleDOI
LPS Pretreatment Attenuates Cerebral Ischaemia/Reperfusion Injury by Inhibiting Inflammation and Apoptosis.
TL;DR: LPS pretreatment significantly ameliorates the effects of cerebral IRI by inhibiting inflammation and apoptosis, and the potential mechanism of the neuroprotective effect may be associated with the ER stress-CHOP mediated signalling pathway.
Journal ArticleDOI
Pharmacologic inhibition of S1P attenuates ATF6 expression, causes ER stress and contributes to apoptotic cell death
TL;DR: It is suggested that S1P plays a crucial role in the regulation of ER folding capacity and also identifies a compensatory cross‐talk between UPR transducers in order to maintain adequate ER chaperone expression and activity.
Posted ContentDOI
LTK is an ER-resident receptor tyrosine kinase that regulates secretion
Federica Grazia Centonze,Veronika Reiterer,Karsten Nalbach,Kota Saito,Krzysztof Pawłowski,Christian Behrends,Hesso Farhan +6 more
TL;DR: LTK-to-Sec12 signaling represents the first example of an ER-resident signaling module the potential to regulate proteostasis and helps gain a deeper understanding of the regulation of ER function and thus of protestasis.
Journal ArticleDOI
Mitochondria Associated Membranes (MAMs): Emerging Drug Targets for Diabetes.
TL;DR: The mechanisms involved in maintaining the contact site are highlighted with new avenues of investigations for the development of novel preventive and therapeutic targets for T2DM.
Journal ArticleDOI
Dexmedetomidine attenuates neuronal injury after spinal cord ischaemia-reperfusion injury by targeting the CNPY2-endoplasmic reticulum stress signalling.
TL;DR: Investigation of whether Dex attenuates spinal cord ischaemia‐reperfusion injury (SCIRI) by inhibiting endoplasmic reticulum stress (ERS) and the results of this study indicate that Dex may attenuate SCIRI by inhibition of the CNPY2‐ERS apoptotic pathway.
References
More filters
Journal ArticleDOI
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.
Related Papers (5)
The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation
Peter Walter,David Ron +1 more
Signal integration in the endoplasmic reticulum unfolded protein response
David Ron,Peter Walter +1 more