An interdomain helix in IRE1α mediates the conformational change required for the sensor's activation

Ricci, Daniela; Tutton, Stephen; Marrocco, Ilaria; Ying, Mingjie; Blumenthal, Daniel S.; Eletto, Daniela; Vargas, Jade; Boyle, Sarah; Fazelinia, Hossein; Qian, Lei; Suresh, Krishna; Taylor, Deanne; Paton, James C.; Paton, Adrienne W.; Tang, Chih-Hang Anthony; Hu, Chih‐Chi Andrew; Radhakrishnan, Ravi; Gidalevitz, Tali; Argon, Yair

doi:10.1016/j.jbc.2021.100781

Cited by 7 publications

(6 citation statements)

References 47 publications

(113 reference statements)

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“…As expected, IRE1-HaloTag exhibited a reticulated distribution characteristic of ER-localized proteins ( Figure 1D ). We were surprised to observe that IRE1-HaloTag did not assemble into large clusters upon induction of ER stress ( Figure 1E ; also see “Detection of Large IRE1 Clusters” in Materials and Methods), in direct contrast to previous work by us and others that relied on ectopic expression of GFP-tagged IRE1 protein ( Li et al, 2010 ; Belyy et al, 2020 ; Ricci et al, 2019 ; Ricci et al, 2021 ; Cohen et al, 2017 ; Wu et al, 2021 ; Li et al, 2020 ). The lack of clustering was not due to a defect of the IRE1-HaloTag fusion construct, since overexpression of the same IRE1-HaloTag protein by transient transfection resulted in readily observed stress-induced clusters ( Figure 1—figure supplement 3 ).…”

Section: Resultscontrasting

confidence: 77%

Endoplasmic reticulum stress activates human IRE1α through reversible assembly of inactive dimers into small oligomers

Belyy

Zuazo-Gaztelu²,

Alamban

et al. 2022

eLife

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Protein folding homeostasis in the endoplasmic reticulum (ER) is regulated by a signaling network, termed the unfolded protein response (UPR). Inositol-requiring enzyme 1 (IRE1) is an ER membrane-resident kinase/RNase that mediates signal transmission in the most evolutionarily conserved branch of the UPR. Dimerization and/or higher-order oligomerization of IRE1 are thought to be important for its activation mechanism, yet the actual oligomeric states of inactive, active, and attenuated mammalian IRE1 complexes remain unknown. We developed an automated two-color single-molecule tracking approach to dissect the oligomerization of tagged endogenous human IRE1 in live cells. In contrast to previous models, our data indicate that IRE1 exists as a constitutive homodimer at baseline and assembles into small oligomers upon ER stress. We demonstrate that the formation of inactive dimers and stress-dependent oligomers is fully governed by IRE1’s lumenal domain. Phosphorylation of IRE1’s kinase domain occurs more slowly than oligomerization and is retained after oligomers disassemble back into dimers. Our findings suggest that assembly of IRE1 dimers into larger oligomers specifically enables trans-autophosphorylation, which in turn drives IRE1’s RNase activity.

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Section: Resultscontrasting

confidence: 77%

Endoplasmic reticulum stress activates human IRE1α through reversible assembly of inactive dimers into small oligomers

Belyy

Zuazo-Gaztelu²,

Alamban

et al. 2022

eLife

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“…In order to minimize the influence of the new circuit on the original instrument, the interface circuit obtains the voltage signal of the original experimental instrument through the emitter-stalk circuit composed of operational amplifiers. Similarly, in order to make the acquisition results consistent with the original experimental instrument, the interface circuit also obtains the reference voltage of the original instrument through the emitter-following circuit as the reference voltage for A/D conversion [19].…”

Section: Research On Various Sensing Technologiesmentioning

confidence: 99%

Design and Implementation of Virtual Simulation Animation Experience Hall Based on VR and Sensing Technology

Luo

2022

Wireless Communications and Mobile Computing

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In order to meet the needs of the design and feasibility of the virtual simulation animation experience hall, the author proposes a research based on VR and sensing technology. The main content of this research is the research of virtual simulation system based on VR and sensing technology, through the analysis of temperature sensing technology, using optical sensing technology and other methods, and finally constructing research methods based on VR and sensing technology through experiments and analysis. Experimental results show that when the light intensity is 0.5 mW, the voltage reaches 3.0 V, and the electrical quantity voltage increases with the increase of the nonelectrical quantity light intensity, which meets the design requirements of the sensor and is feasible for the design and implementation of the virtual simulation animation experience hall. Conclusion. The research based on VR and sensing technology can meet the needs of the design and implementation of the virtual simulation animation experience hall.

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“…It’s categorized as a type I transmembrane protein with dual functionalities, serving as both an endoribonuclease and a serine/threonine kinase. When GRP78 disengages, IRE1α experiences homo-oligomerization and trans-autophosphorylation events, which then activate its endoribonuclease and kinase domains ( Ricci et al, 2021 ). As a result of this activation, IRE1α becomes engaged in facilitating the splicing of the mRNA intron responsible for encoding XBP1.…”

Section: Endoplasmic Reticulum Stress and Apoptosismentioning

confidence: 99%

Orexins in apoptosis: a dual regulatory role

Cavalu,

Saber,

Hamad

et al. 2024

Front. Cell. Neurosci.

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The orexins, also referred to as hypocretins, are neuropeptides that originate from the lateral hypothalamus (LH) region of the brain. They are composed of two small peptides, orexin-A, and orexin-B, which are broadly distributed throughout the central and peripheral nervous systems. Orexins are recognized to regulate diverse functions, involving energy homeostasis, the sleep-wake cycle, stress responses, and reward-seeking behaviors. Additionally, it is suggested that orexin-A deficiency is linked to sleepiness and narcolepsy. The orexins bind to their respective receptors, the orexin receptor type 1 (OX1R) and type 2 (OX2R), and activate different signaling pathways, which results in the mediation of various physiological functions. Orexin receptors are widely expressed in different parts of the body, including the skin, muscles, lungs, and bone marrow. The expression levels of orexins and their receptors play a crucial role in apoptosis, which makes them a potential target for clinical treatment of various disorders. This article delves into the significance of orexins and orexin receptors in the process of apoptosis, highlighting their expression levels and their potential contributions to different diseases. The article offers an overview of the existing understanding of the orexin/receptor system and how it influences the regulation of apoptosis.

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An interdomain helix in IRE1α mediates the conformational change required for the sensor's activation

Cited by 7 publications

References 47 publications

Endoplasmic reticulum stress activates human IRE1α through reversible assembly of inactive dimers into small oligomers

Endoplasmic reticulum stress activates human IRE1α through reversible assembly of inactive dimers into small oligomers

Design and Implementation of Virtual Simulation Animation Experience Hall Based on VR and Sensing Technology

Orexins in apoptosis: a dual regulatory role

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