Genome-wide RNAi screen and in vivo protein aggregation reporters identify degradation of damaged proteins as an essential hypertonic stress response

Choe, Keith P.; Strange, Kevin

doi:10.1152/ajpcell.00450.2008

Cited by 67 publications

(106 citation statements)

References 66 publications

Supporting

Mentioning

101

Contrasting

Order By: Relevance

“…Remarkably, over 90% of individual C. elegans can survive direct transfer from 51 up to 400 mM NaCl (17)(18)(19)107). Approximate timing of physiological changes that occur following direct transfer to extreme hypertonicity is shown in Fig.…”

Section: Volume Recovery and Wnk/gck VI Signalingmentioning

confidence: 99%

“…After the screen for regulators of gpdh-1, a separate genomewide RNAi screen was performed to identify genes that are required for survival of acute hypertonic stress (17). Silencing of 40 genes was found to strongly sensitize C. elegans to hypertonic stress.…”

Section: Protein Damage As a Sensor And Principle Determinant Of Hypementioning

confidence: 99%

“…However, the fate of proteins during hypertonic stress is largely unknown for intact animal cells, which have complex mixtures of macromolecules, are divided into distinct compartments, and maintain dynamic and active mechanisms of protein turnover and quality control. A strain of worm expressing a fluorescent reporter protein containing an aggregation-prone 35 glutamine repeat was used to demonstrate that cell shrinkage promotes protein aggregation in vivo (17). Transfer of worms to high osmolarity agar plates containing the impermeable solutes NaCl or sorbitol (made with equal total osmotic pressures) caused similar levels of whole-animal shrinkage and aggregation.…”

Section: Protein Damage As a Sensor And Principle Determinant Of Hypementioning

confidence: 99%

“…Transfer of worms to high osmolarity agar plates containing the impermeable solutes NaCl or sorbitol (made with equal total osmotic pressures) caused similar levels of whole-animal shrinkage and aggregation. Alternatively, transfer to agar with high concentrations of the more permeable protein denaturant urea did not, suggesting that conditions associated with cell shrinkage, such as macromolecular crowding, cause aggregation (17) (Fig. 5).…”

Section: Protein Damage As a Sensor And Principle Determinant Of Hypementioning

confidence: 99%

“…This acclimation response also decreases hypertonicity-induced aggregation of the polyglutamine reporter, implying that acclimation could be the result of enhanced protein homeostasis (17). A series of experiments were conducted to investigate mechanisms of acclimation (14).…”

Section: Protein Damage As a Sensor And Principle Determinant Of Hypementioning

confidence: 99%

See 4 more Smart Citations

Physiological and molecular mechanisms of salt and water homeostasis in the nematodeCaenorhabditis elegans

Choe

2013

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

View full text Add to dashboard Cite

Choe KP. Physiological and molecular mechanisms of salt and water homeostasis in the nematode Caenorhabditis elegans. Am J Physiol Regul Integr Comp Physiol 305: R175-R186, 2013. First published June 5, 2013 doi:10.1152/ajpregu.00109.2013.-Intracellular salt and water homeostasis is essential for all cellular life. Extracellular salt and water homeostasis is also important for multicellular organisms. Many fundamental mechanisms of compensation for osmotic perturbations are well defined and conserved. Alternatively, molecular mechanisms of detecting salt and water imbalances and regulating compensatory responses are generally poorly defined for animals. Throughout the last century, researchers studying vertebrates and vertebrate cells made critical contributions to our understanding of osmoregulation, especially mechanisms of salt and water transport and organic osmolyte accumulation. Researchers have more recently started using invertebrate model organisms with defined genomes and well-established methods of genetic manipulation to begin defining the genes and integrated regulatory networks that respond to osmotic stress. The nematode Caenorhabditis elegans is well suited to these studies. Here, I introduce osmoregulatory mechanisms in this model, discuss experimental advantages and limitations, and review important findings. Key discoveries include defining genetic mechanisms of osmolarity sensing in neurons, identifying protein damage as a sensor and principle determinant of hypertonic stress resistance, and identification of a putative sensor for hypertonic stress associated with the extracellular matrix. Many of these processes and pathways are conserved and, therefore, provide new insights into salt and water homeostasis in other animals, including mammals. osmoregulation; cell volume; ion; organic osmolyte; protein homeostasis; model organism SALT AND WATER HOMEOSTASIS is a fundamental requirement for metazoan life. Ion and water transport mechanisms that compensate for changes in composition and volume of intracellular and extracellular compartments have been generally well defined using vertebrate cell and in vivo models (38). Alternatively, the upstream molecular mechanisms that animal cells use to sense deviations in salt and water balance and regulate compensatory responses are still poorly characterized (20). Studies in brewer's yeast demonstrate that osmotic signal detection and transduction within a single eukaryotic cell can be highly complex with numerous components, acting in parallel pathways, that often cross-talk with other processes (40,55). Osmotic signal detection and transduction are likely to be even more complex in metazoans, which require homeostasis of both the extracellular and intracellular compartments and integration of responses between cells. Genetics is an extremely powerful approach for identifying and characterizing genes and proteins that function in complex biological processes but has been underutilized in the field of osmosensing and signal transduction in metazoans. In...

show abstract

Section: Volume Recovery and Wnk/gck VI Signalingmentioning

confidence: 99%

Section: Protein Damage As a Sensor And Principle Determinant Of Hypementioning

confidence: 99%

Section: Protein Damage As a Sensor And Principle Determinant Of Hypementioning

confidence: 99%

Section: Protein Damage As a Sensor And Principle Determinant Of Hypementioning

confidence: 99%

Section: Protein Damage As a Sensor And Principle Determinant Of Hypementioning

confidence: 99%

See 3 more Smart Citations

Physiological and molecular mechanisms of salt and water homeostasis in the nematodeCaenorhabditis elegans

Choe

2013

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

View full text Add to dashboard Cite

show abstract

Differential response of nucleus pulposus intervertebral disc cells to high salt, sorbitol, and urea

Mavrogonatou

Kletsas

2011

Journal Cellular Physiology

View full text Add to dashboard Cite

Nucleus pulposus intervertebral disc cells are routinely confronted with high osmolality in their microenvironment and respond to this stress in vitro by regulating cell cycle progression and by activating a DNA repair machinery in order to counteract its genotoxic effect. In the present study, we attempted to identify the origin of this osmo-regulatory response, by using an ionic NaCl/KCl solution, the compatible osmolyte sorbitol, and the readily permeant urea. High salt and sorbitol were found to activate similar molecular pathways, including the p38 MAPK and the p53-p21(WAF1)-pRb axis, that were not stimulated by high urea. On the other hand, only high urea led to the phosphorylation of ERKs and JNKs. Furthermore, salt- and sorbitol-treated cells were able to phosphorylate histone H2A.X on Ser139, in contrast to cells exposed to urea, indicating a common mechanism for DNA repair, which was achieved by a p53-dependent activation of the G1 checkpoint by both solutes. DNA repair, as directly measured by a host cell reactivation assay, occurred under conditions of hyperosmolar salt and sorbitol, although to a lesser extent in sorbitol-treated cells than in cells exposed to high salinity. Taken as a whole, our findings suggest that the hyperosmolality-provoked DNA damage and the responses of nucleus pulposus cells induced by this genotoxic stress most probably originate from cell volume alterations mediated by hypertonicity and not from increased intracellular ionic concentration.

show abstract

Freshwater Acclimation Induces Stress Responses and Expression of Branchial Na⁺/K⁺‐ATPase and Proliferating Cell Nuclear Antigen in Takifugu niphobles

Tang

Lee

2013

J. Exp. Zool.

View full text Add to dashboard Cite

Almost the whole life cycle of the grass puffer (Takifugu niphobles) occurs in seawater (SW), but it is also sometimes found in fresh water (FW) rivers. This study aims to evaluate the effects of FW exposure on the stress, osmoregulatory, and physiological responses of the grass puffer. The grass puffers were captured from a local wetland and acclimated to SW (35‰) or FW in the laboratory. In the stress responses, plasma glucose concentrations and the abundances of hepatic and branchial heat shock proteins were higher in the FW group than in the SW group. FW acclimation led to a significant increase in the protein abundance and the specific activity of branchial Na(+)/K(+)-ATPase (NKA). Immunochemical staining showed that the NKA immunoreactive (NKIR) cells of the FW and SW puffer were distributed mainly in gill filaments. Although the number of NKIR cells was similar in the two groups, the protein levels of proliferating cell nuclear antigen (PCNA) of nuclear fractions were elevated in the gills of the FW puffer. The induction of gill PCNA might contribute to cell proliferation which would maintain the amount of NKIR cells or repair DNA when exposed to FW, an osmotically stressful environment. Hence, activation of stress responses would provide the osmoprotection associated with FW adaptation of the grass puffer. Changes of branchial NKA expression and activity for osmoregulatory adjustment were required for stable blood osmolality and muscle water content. Based on our findings, the grass puffer was suggested to be a euryhaline teleost with SW preference.

show abstract

Genome-wide RNAi screen and in vivo protein aggregation reporters identify degradation of damaged proteins as an essential hypertonic stress response

Cited by 67 publications

References 66 publications

Physiological and molecular mechanisms of salt and water homeostasis in the nematodeCaenorhabditis elegans

Physiological and molecular mechanisms of salt and water homeostasis in the nematodeCaenorhabditis elegans

Differential response of nucleus pulposus intervertebral disc cells to high salt, sorbitol, and urea

Freshwater Acclimation Induces Stress Responses and Expression of Branchial Na⁺/K⁺‐ATPase and Proliferating Cell Nuclear Antigen in Takifugu niphobles

Contact Info

Product

Resources

About

Genome-wide RNAi screen and in vivo protein aggregation reporters identify degradation of damaged proteins as an essential hypertonic stress response

Cited by 67 publications

References 66 publications

Physiological and molecular mechanisms of salt and water homeostasis in the nematodeCaenorhabditis elegans

Physiological and molecular mechanisms of salt and water homeostasis in the nematodeCaenorhabditis elegans

Differential response of nucleus pulposus intervertebral disc cells to high salt, sorbitol, and urea

Freshwater Acclimation Induces Stress Responses and Expression of Branchial Na+/K+‐ATPase and Proliferating Cell Nuclear Antigen in Takifugu niphobles

Contact Info

Product

Resources

About

Freshwater Acclimation Induces Stress Responses and Expression of Branchial Na⁺/K⁺‐ATPase and Proliferating Cell Nuclear Antigen in Takifugu niphobles