An intact IRE1 transmembrane domain is necessary for UPR activation upon lipid bilayer stress in S. cerevisiae

Membrane integrity at the endoplasmic reticulum (ER) is compromised in metabolic diseases. Recently, it became evident that such ER lipid aberrations activate the unfolded protein response (UPRLBS). Using a truncated form of the UPR sensor Ire1 that is responsive solely to changes in lipid bilayer c...

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Main Author: Ho, Nurulain
Other Authors: Guillaume Thibault
Format: Thesis-Doctor of Philosophy
Language:English
Published: Nanyang Technological University 2020
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Online Access:https://hdl.handle.net/10356/137434
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1374342023-02-28T18:49:15Z An intact IRE1 transmembrane domain is necessary for UPR activation upon lipid bilayer stress in S. cerevisiae Ho, Nurulain Guillaume Thibault School of Biological Sciences thibault@ntu.edu.sg Science::Biological sciences Membrane integrity at the endoplasmic reticulum (ER) is compromised in metabolic diseases. Recently, it became evident that such ER lipid aberrations activate the unfolded protein response (UPRLBS). Using a truncated form of the UPR sensor Ire1 that is responsive solely to changes in lipid bilayer composition, we identified pathways, beyond lipid metabolism, required to maintain ER integrity. A lipid sensing switch within the amphipathic helix of Ire1 revealed the importance of the transmembrane domain as a sensor to lipid bilayer stress (LBS). An exciting outcome of our transcriptomic and ChIP-qPCR data confirm novel genes upregulated solely by UPRLBS suggesting an alternative transcriptional programme activated for the adaptation of cells during LBS. This work establishes the broad extent of the UPR, providing insights for future therapeutic interventions. Doctor of Philosophy 2020-03-25T07:32:26Z 2020-03-25T07:32:26Z 2019 Thesis-Doctor of Philosophy Ho, N. (2019). An intact IRE1 transmembrane domain is necessary for UPR activation upon lipid bilayer stress in S. cerevisiae. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/137434 10.32657/10356/137434 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
spellingShingle Science::Biological sciences
Ho, Nurulain
An intact IRE1 transmembrane domain is necessary for UPR activation upon lipid bilayer stress in S. cerevisiae
description Membrane integrity at the endoplasmic reticulum (ER) is compromised in metabolic diseases. Recently, it became evident that such ER lipid aberrations activate the unfolded protein response (UPRLBS). Using a truncated form of the UPR sensor Ire1 that is responsive solely to changes in lipid bilayer composition, we identified pathways, beyond lipid metabolism, required to maintain ER integrity. A lipid sensing switch within the amphipathic helix of Ire1 revealed the importance of the transmembrane domain as a sensor to lipid bilayer stress (LBS). An exciting outcome of our transcriptomic and ChIP-qPCR data confirm novel genes upregulated solely by UPRLBS suggesting an alternative transcriptional programme activated for the adaptation of cells during LBS. This work establishes the broad extent of the UPR, providing insights for future therapeutic interventions.
author2 Guillaume Thibault
author_facet Guillaume Thibault
Ho, Nurulain
format Thesis-Doctor of Philosophy
author Ho, Nurulain
author_sort Ho, Nurulain
title An intact IRE1 transmembrane domain is necessary for UPR activation upon lipid bilayer stress in S. cerevisiae
title_short An intact IRE1 transmembrane domain is necessary for UPR activation upon lipid bilayer stress in S. cerevisiae
title_full An intact IRE1 transmembrane domain is necessary for UPR activation upon lipid bilayer stress in S. cerevisiae
title_fullStr An intact IRE1 transmembrane domain is necessary for UPR activation upon lipid bilayer stress in S. cerevisiae
title_full_unstemmed An intact IRE1 transmembrane domain is necessary for UPR activation upon lipid bilayer stress in S. cerevisiae
title_sort intact ire1 transmembrane domain is necessary for upr activation upon lipid bilayer stress in s. cerevisiae
publisher Nanyang Technological University
publishDate 2020
url https://hdl.handle.net/10356/137434
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