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Stress sensor Ire1 deploys a divergent transcriptional program in response to lipid bilayer stress.
- Source :
-
The Journal of cell biology [J Cell Biol] 2020 Jul 06; Vol. 219 (7). - Publication Year :
- 2020
-
Abstract
- Membrane integrity at the endoplasmic reticulum (ER) is tightly regulated, and its disturbance is implicated in metabolic diseases. Using an engineered sensor that activates the unfolded protein response (UPR) exclusively when normal ER membrane lipid composition is compromised, we identified pathways beyond lipid metabolism that are necessary to maintain ER integrity in yeast and in C. elegans. To systematically validate yeast mutants that disrupt ER membrane homeostasis, we identified a lipid bilayer stress (LBS) sensor in the UPR transducer protein Ire1, located at the interface of the amphipathic and transmembrane helices. Furthermore, transcriptome and chromatin immunoprecipitation analyses pinpoint the UPR as a broad-spectrum compensatory response wherein LBS and proteotoxic stress deploy divergent transcriptional UPR programs. Together, these findings reveal the UPR program as the sum of two independent stress responses, an insight that could be exploited for future therapeutic intervention.<br /> (© 2020 Ho et al.)
- Subjects :
- Animals
Biosensing Techniques
Caenorhabditis elegans metabolism
Caenorhabditis elegans Proteins metabolism
Chromatin chemistry
Chromatin metabolism
Endoplasmic Reticulum
Gene Expression Profiling
Gene Expression Regulation
Genes, Reporter
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
Heat-Shock Proteins metabolism
Homeostasis genetics
Intracellular Membranes metabolism
Intracellular Membranes ultrastructure
Lipid Bilayers metabolism
Lipid Metabolism genetics
Luminescent Proteins genetics
Luminescent Proteins metabolism
Membrane Glycoproteins metabolism
Protein Serine-Threonine Kinases metabolism
Saccharomyces cerevisiae metabolism
Saccharomyces cerevisiae Proteins metabolism
Transcription, Genetic
Red Fluorescent Protein
Caenorhabditis elegans genetics
Caenorhabditis elegans Proteins genetics
Endoplasmic Reticulum Stress genetics
Heat-Shock Proteins genetics
Lipid Bilayers chemistry
Membrane Glycoproteins genetics
Protein Serine-Threonine Kinases genetics
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae Proteins genetics
Unfolded Protein Response
Subjects
Details
- Language :
- English
- ISSN :
- 1540-8140
- Volume :
- 219
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- The Journal of cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 32349127
- Full Text :
- https://doi.org/10.1083/jcb.201909165