Dataset Information

Cellular Proteomes Drive Tissue-Specific Regulation of the Heat Shock Response.

ABSTRACT: The heat shock response (HSR) is a cellular stress response that senses protein misfolding and restores protein folding homeostasis, or proteostasis. We previously identified an HSR regulatory network in Caenorhabditis elegans consisting of highly conserved genes that have important cellular roles in maintaining proteostasis. Unexpectedly, the effects of these genes on the HSR are distinctly tissue-specific. Here, we explore this apparent discrepancy and find that muscle-specific regulation of the HSR by the TRiC/CCT chaperonin is not driven by an enrichment of TRiC/CCT in muscle, but rather by the levels of one of its most abundant substrates, actin. Knockdown of actin subunits reduces induction of the HSR in muscle upon TRiC/CCT knockdown; conversely, overexpression of an actin subunit sensitizes the intestine so that it induces the HSR upon TRiC/CCT knockdown. Similarly, intestine-specific HSR regulation by the signal recognition particle (SRP), a component of the secretory pathway, is driven by the vitellogenins, some of the most abundant secretory proteins. Together, these data indicate that the specific protein folding requirements from the unique cellular proteomes sensitizes each tissue to disruption of distinct subsets of the proteostasis network. These findings are relevant for tissue-specific, HSR-associated human diseases such as cancer and neurodegenerative diseases. Additionally, we characterize organismal phenotypes of actin overexpression including a shortened lifespan, supporting a recent hypothesis that maintenance of the actin cytoskeleton is an important factor for longevity.

SUBMITTER: Ma J

PROVIDER: S-EPMC5345702 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Cellular Proteomes Drive Tissue-Specific Regulation of the Heat Shock Response.

Ma Jian J Grant Christopher E CE Plagens Rosemary N RN Barrett Lindsey N LN Kim Guisbert Karen S KS Guisbert Eric E

G3 (Bethesda, Md.) 20170310 3

The heat shock response (HSR) is a cellular stress response that senses protein misfolding and restores protein folding homeostasis, or proteostasis. We previously identified an HSR regulatory network in <i>Caenorhabditis elegans</i> consisting of highly conserved genes that have important cellular roles in maintaining proteostasis. Unexpectedly, the effects of these genes on the HSR are distinctly tissue-specific. Here, we explore this apparent discrepancy and find that muscle-specific regulati ...[more]

PMID: 28143946

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Project description:The majority of fungal species prefer the 12° to 30°C range, and relatively few species tolerate temperatures higher than 35°C. Our understanding of the mechanisms underpinning the ability of some species to grow at higher temperatures is incomplete. Nosema ceranae is an obligate intracellular fungal parasite that infects honey bees and can cause individual mortality and contribute to colony collapse. Despite a reduced genome, this species is strikingly thermotolerant, growing optimally at the colony temperature of 35°C. In characterizing the heat shock response (HSR) in N. ceranae, we found that this and other microsporidian species have lost the transcriptional regulator HSF and possess a reduced set of putative core HSF1-dependent HSR target genes. Despite these losses, N. ceranae demonstrates robust upregulation of the remaining HSR target genes after heat shock. In addition, thermal stress leads to alterations in genes involved in various metabolic pathways, ribosome biogenesis and translation, and DNA repair. These results provide important insight into the stress responses of microsporidia. Such a new understanding will allow new comparisons with other pathogenic fungi and potentially enable the discovery of novel treatment strategies for microsporidian infections affecting food production and human health.IMPORTANCE We do not fully understand why some fungal species are able to grow at temperatures approaching mammalian body temperature. Nosema ceranae, a microsporidium, is a type of fungal parasite that infects honey bees and grows optimally at the colony temperature of 35°C despite possessing cellular machinery for responding to heat stress that is notably simpler than that of other fungi. We find that N. ceranae demonstrates a robust and broad response to heat shock. These results provide important insight into the stress responses of this type of fungus, allow new comparisons with other pathogenic fungi, and potentially enable the discovery of novel treatment strategies for this type of fungus.

Dataset Information

Cellular Proteomes Drive Tissue-Specific Regulation of the Heat Shock Response.

Publications

Cellular Proteomes Drive Tissue-Specific Regulation of the Heat Shock Response.

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