ArticleAmerican journal of physiology. Cell physiology2008
Genome-wide RNAi screen and in vivo protein aggregation reporters identify degradation of damaged proteins as an essential hypertonic stress response.
Article in American journal of physiology. Cell physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 75 citations in OpenAlex.
- Rapid activation of p62 body-mediated autophagy in human cells under hyperosmotic stress.Communications biology · 2026Article
- Protein aggregation as a bistable switch in bacterial cell fate: from adaptive dormancy to cytotoxic death.Frontiers in microbiology · 2026Review
- Soma to neuron communication links stress adaptation to stress avoidance behavior.bioRxiv : the preprint server for biology · 2025Article
- An enteric neuron-expressed variant ionotropic receptor detects ingested salts to regulate salt stress resistance.bioRxiv : the preprint server for biology · 2025Article
- A safety mechanism enables tissue-specific resistance to protein aggregation during aging in C. elegans.PLoS biology · 2023Article
- When Phased without Water: Biophysics of Cellular Desiccation, from Biomolecules to Condensates.Chemical reviews · 2023Review
- Article
- Disexcitation in the ASH/RIM/ADL negative feedback circuit fine-tunes hyperosmotic sensation and avoidance inFrontiers in molecular neuroscience · 2023Article
- Identification of healthspan-promoting genes in Caenorhabditis elegans based on a human GWAS study.Biogerontology · 2022Article
- CRYPTOCHROMES promote daily protein homeostasis.The EMBO journal · 2022Article
- Deciphering the mechanism of anhydrobiosis in the entomopathogenic nematode Heterorhabditis indica through comparative transcriptomics.PloS one · 2022Article
- Article
- The C. elegans Hypertonic Stress Response: Big Insights from Shrinking Worms.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2021Review
- Automated phenotyping ofMicrosystems & nanoengineering · 2020Article
- HIF1A and NFAT5 coordinate NaAutophagy · 2019Article
- Osmotic Demyelination: From an Oligodendrocyte to an Astrocyte Perspective.International journal of molecular sciences · 2019Review
- The Stress-Chip: A microfluidic platform for stress analysis in Caenorhabditis elegans.PloS one · 2019Article
- A field and laboratory study of the responses of cytoprotection and osmoregulation to salinity stress in mosquitofish (Gambusia affinis).Fish physiology and biochemistry · 2018Article
- The role of declining adaptive homeostasis in ageing.The Journal of physiology · 2017Review
- Osmotic Stress-Induced Defective Glial Proteostasis Contributes to Brain Demyelination after Hyponatremia Treatment.Journal of the American Society of Nephrology : JASN · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The damaging effects of hypertonic stress on cellular proteins are poorly defined, and almost nothing is known about the pathways that detect and repair hypertonicity-induced protein damage. To begin addressing these problems, we screened approximately 19,000 Caenorhabditis elegans genes by RNA interference (RNAi) feeding and identified 40 that are essential for survival during acute hypertonic stress. Half (20 of 40) of these genes encode proteins that function to detect, transport, and degrade damaged proteins, including components of the ubiquitin-proteasome system, endosomal sorting complexes, and lysosomes. High-molecular-weight ubiquitin conjugates increase during hypertonic stress, suggesting a global change in the ubiquitinylation state of endogenous proteins. Using a polyglutamine-containing fluorescent reporter, we demonstrate that cell shrinkage induces rapid protein aggregation in vivo and that many of the genes that are essential for survival during hypertonic stress function to prevent accumulation of aggregated proteins. High levels of urea, a strong protein denaturant, do not cause aggregation, suggesting that factors such as macromolecular crowding also contribute to protein aggregate formation during cell shrinkage. Acclimation of C. elegans to mild hypertonicity dramatically increases the osmotic threshold for protein aggregation, demonstrating that protein aggregation-inhibiting pathways are activated by osmotic stress. Our studies demonstrate that hypertonic stress induces protein damage in vivo and that detection and degradation of damaged proteins are essential mechanisms for survival under hypertonic conditions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.