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...
Saved in:
Main Author: | |
---|---|
Other Authors: | |
Format: | Thesis-Doctor of Philosophy |
Language: | English |
Published: |
Nanyang Technological University
2020
|
Subjects: | |
Online Access: | https://hdl.handle.net/10356/137434 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Nanyang Technological University |
Language: | English |
id |
sg-ntu-dr.10356-137434 |
---|---|
record_format |
dspace |
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 |
_version_ |
1759857800442281984 |