CCAR-1 is a negative regulator of the heat-shock response in Caenorhabditis elegans

AbstractThe heat shock response is the organized molecular response to stressors which disrupt proteostasis, potentially leading to protein misfolding and aggregation. While the regulation of the heat shock response is well-studied in single cells, its coordination at the cell, tissue, and systemic levels of a multicellular organism is poorly understood. To probe the interplay between systemic and cell-autonomous responses, we studied the upregulation of HSP-16.2, a molecular chaperone induced throughout the intestine of Caenorhabditis elegans following a heat shock, by taking longitudinal measurements in a microfluidic environment. Based on the dynamics of HSP-16.2 accumulation, we showed that a combination of heat shock temperature and duration define the intensity of stress inflicted on the worm and identified two regimes of low and high intensity stress. Modeling the underlying regulatory dynamics implicated the saturation of heat shock protein mRNA production in defining these two regimes and emphasized the importance of time separation between transcription and translation in establishing these dynamics. By applying a heat shock and measuring the response in separate parts of the animals, we implicated thermosensory neurons in accelerating the response and transducing information within the animal. We discuss possible implications of the systemic and cell level aspects and how they coordinate to facilitate the organismal response.

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Cytosol-Localized Heat Shock Factor-Binding Protein, AtHSBP, Functions as a Negative Regulator of Heat Shock Response by Translocation to the Nucleus and Is Required for Seed Development in Arabidopsis

PLANT PHYSIOLOGY ◽

10.1104/pp.109.151225 ◽

2010 ◽

Vol 153 (2) ◽

pp. 773-784 ◽

Cited By ~ 38

Author(s):

Shih-Feng Hsu ◽

Hui-Chuan Lai ◽

Tsung-Luo Jinn

Keyword(s):

Heat Shock ◽

Seed Development ◽

Heat Shock Response ◽

Binding Protein ◽

Heat Shock Factor ◽

Negative Regulator ◽

Factor Binding ◽

Shock Response

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Identification of a Novel cis-Regulatory Element Involved in the Heat Shock Response in Caenorhabditis elegans Using Microarray Gene Expression and Computational Methods

Genome Research ◽

10.1101/gr.228902 ◽

2002 ◽

Vol 12 (5) ◽

pp. 701-712 ◽

Cited By ~ 95

Author(s):

D. GuhaThakurta

Keyword(s):

Gene Expression ◽

Caenorhabditis Elegans ◽

Heat Shock ◽

Computational Methods ◽

Heat Shock Response ◽

Regulatory Element ◽

Microarray Gene Expression ◽

Shock Response ◽

Microarray Gene

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Systemic activation coordinates the heat shock response of the insulin/IGF-1 pathway in Caenorhabditis elegans

10.1101/131375 ◽

2017 ◽

Author(s):

Ronen B Kopito ◽

Kathie Watkins ◽

Erel Levine

Keyword(s):

Caenorhabditis Elegans ◽

Stress Response ◽

Heat Shock ◽

Heat Shock Response ◽

Cellular Response ◽

Precise Control ◽

Cellular Processes ◽

Shock Response ◽

Stressed Cells ◽

Shock Proteins

Exposure to high temperatures has an adverse effect on cellular processes and results in activation of the cellular heat shock response (HSR), a highly conserved program of inducible genes to maintain protein homeostasis1. The insulin/IGF-1 signaling (IIS) pathway, which has diverse roles from metabolism to stress response and longevity, is activated as part of the HSR2–4. Recent evidence suggest that the IIS pathway is able to affect proteostasis non-autonomously5,6, yet it is not known if it is activated autonomously in stressed cells or systemically as part of an organismic program. In Caenorhabditis elegans, the single forkhead box O (FOXO) homologue DAF-16 functions as the major target of the IIS pathway7 and, together with the heat-shock factor HSF-1, induce the expression of small heat shock proteins in response to heat shock8–10,3. Here we use a novel microfluidic device that allows precise control of the spatiotemporal temperature profile to show that cellular activation of DAF-16 integrates local temperature sensation with systemic signals. We demonstrate that DAF-16 activation in head sensory neurons is essential for DAF-16 activation in other tissues, but show that no known thermosensory neuron is individually required. Our findings demonstrate that systemic and cell-autonomous aspects of stress response act together to facilitate a coordinated cellular response at the organismic level.

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Diverse roles for HspR in Campylobacter jejuni revealed by the proteome, transcriptome and phenotypic characterization of an hspR mutant

Microbiology ◽

10.1099/mic.0.27513-0 ◽

2005 ◽

Vol 151 (3) ◽

pp. 905-915 ◽

Cited By ~ 36

Author(s):

Marianne Thorup Andersen ◽

Lone Brøndsted ◽

Bruce M. Pearson ◽

Francis Mulholland ◽

Mary Parker ◽

...

Keyword(s):

Heat Shock ◽

Campylobacter Jejuni ◽

Heat Shock Response ◽

Negative Regulator ◽

Phenotypic Characterization ◽

Heat Sensitivity ◽

Altered Expression ◽

Shock Response ◽

Mutant Cells

Campylobacter jejuni is a leading cause of bacterial gastroenteritis in the developed world. The role of a homologue of the negative transcriptional regulatory protein HspR, which in other organisms participates in the control of the heat-shock response, was investigated. Following inactivation of hspR in C. jejuni, members of the HspR regulon were identified by DNA microarray transcript profiling. In agreement with the predicted role of HspR as a negative regulator of genes involved in the heat-shock response, it was observed that the transcript amounts of 13 genes were increased in the hspR mutant, including the chaperone genes dnaK, grpE and clpB, and a gene encoding the heat-shock regulator HrcA. Proteomic analysis also revealed increased synthesis of the heat-shock proteins DnaK, GrpE, GroEL and GroES in the absence of HspR. The altered expression of chaperones was accompanied by heat sensitivity, as the hspR mutant was unable to form colonies at 44 °C. Surprisingly, transcriptome analysis also revealed a group of 17 genes with lower transcript levels in the hspR mutant. Of these, eight were predicted to be involved in the formation of the flagella apparatus, and the decreased expression is likely to be responsible for the reduced motility and ability to autoagglutinate that was observed for hspR mutant cells. Electron micrographs showed that mutant cells were spiral-shaped and carried intact flagella, but were elongated compared to wild-type cells. The inactivation of hspR also reduced the ability of Campylobacter to adhere to and invade human epithelial INT-407 cells in vitro, possibly as a consequence of the reduced motility or lower expression of the flagellar export apparatus in hspR mutant cells. It was concluded that, in C. jejuni, HspR influences the expression of several genes that are likely to have an impact on the ability of the bacterium to successfully survive in food products and subsequently infect the consumer.

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