Identification of a tissue-selective heat shock response regulatory network

The heat shock response (HSR) is essential to survive acute proteotoxic stress and has been studied extensively in unicellular organisms and tissue culture cells, but to a lesser extent in intact metazoan animals. To identify the regulatory pathways that control the HSR in Caenorhabditis elegans, we...

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Bibliographic Details
Published in:PLoS genetics 2013-04, Vol.9 (4), p.e1003466-e1003466
Main Authors: Guisbert, Eric, Czyz, Daniel M, Richter, Klaus, McMullen, Patrick D, Morimoto, Richard I
Format: Article
Language:English
Subjects:
Anatomy & physiology
Animals
Biology
Caenorhabditis elegans
Caenorhabditis elegans - metabolism
Excretory system
Experiments
Genetic aspects
Genetics
Genomes
Health aspects
Heat shock proteins
Heat-Shock Proteins - genetics
Heat-Shock Response - genetics
Microbial genetics
Mutation
Organisms
Physiological aspects
Protein Folding
Proteins - genetics
Regulation
RNA Interference
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Summary:The heat shock response (HSR) is essential to survive acute proteotoxic stress and has been studied extensively in unicellular organisms and tissue culture cells, but to a lesser extent in intact metazoan animals. To identify the regulatory pathways that control the HSR in Caenorhabditis elegans, we performed a genome-wide RNAi screen and identified 59 genes corresponding to 7 positive activators required for the HSR and 52 negative regulators whose knockdown leads to constitutive activation of the HSR. These modifiers function in specific steps of gene expression, protein synthesis, protein folding, trafficking, and protein clearance, and comprise the metazoan heat shock regulatory network (HSN). Whereas the positive regulators function in all tissues of C. elegans, nearly all of the negative regulators exhibited tissue-selective effects. Knockdown of the subunits of the proteasome strongly induces HS reporter expression only in the intestine and spermatheca but not in muscle cells, while knockdown of subunits of the TRiC/CCT chaperonin induces HS reporter expression only in muscle cells. Yet, both the proteasome and TRiC/CCT chaperonin are ubiquitously expressed and are required for clearance and folding in all tissues. We propose that the HSN identifies a key subset of the proteostasis machinery that regulates the HSR according to the unique functional requirements of each tissue.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1003466