Heat shock factor-1 intertwines insulin/IGF-1, TGF-beta and cGMP signaling to control development and aging

János Barna, Andrea Princz, Mónika Kosztelnik, Balázsázs Hargitai, K. Takács-Vellai, T. Vellai

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background: Temperature affects virtually all cellular processes. A quick increase in temperature challenges the cells to undergo a heat shock response to maintain cellular homeostasis. Heat shock factor-1 (HSF-1) functions as a major player in this response as it activates the transcription of genes coding for molecular chaperones (also called heat shock proteins) that maintain structural integrity of proteins. However, the mechanisms by which HSF-1 adjusts fundamental cellular processes such as growth, proliferation, differentiation and aging to the ambient temperature remain largely unknown. Results: We demonstrate here that in Caenorhabditis elegans HSF-1 represses the expression of daf-7 encoding a TGF-beta (transforming growth factor-beta) ligand, to induce young larvae to enter the dauer stage, a developmentally arrested, non-feeding, highly stress-resistant, long-lived larval form triggered by crowding and starvation. Under favorable conditions, HSF-1 is inhibited by crowding pheromone-sensitive guanylate cyclase/cGMP (cyclic guanosine monophosphate) and systemic nutrient-sensing insulin/IGF-1 (insulin-like growth factor-1) signaling; loss of HSF-1 activity allows DAF-7 to promote reproductive growth. Thus, HSF-1 interconnects the insulin/IGF-1, TGF-beta and cGMP neuroendocrine systems to control development and longevity in response to diverse environmental stimuli. Furthermore, HSF-1 upregulates another TGF-beta pathway-interacting gene, daf-9/cytochrome P450, thereby fine-tuning the decision between normal growth and dauer formation. Conclusion: Together, these results provide mechanistic insight into how temperature, nutrient availability and population density coordinately influence development, lifespan, behavior and stress response through HSF-1.

Original languageEnglish
Pages (from-to)32
Number of pages1
JournalBMC Developmental Biology
DOIs
Publication statusAccepted/In press - Nov 1 2012

Fingerprint

Insulin-Like Growth Factor I
Transforming Growth Factor beta
Shock
Hot Temperature
Insulin
Heat-Shock Response
Crowding
Temperature
Growth
Food
Neurosecretory Systems
Molecular Chaperones
Guanylate Cyclase
Pheromones
Cyclic GMP
Caenorhabditis elegans
Somatomedins
Heat-Shock Proteins
Population Density
Starvation

ASJC Scopus subject areas

  • Developmental Biology

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Heat shock factor-1 intertwines insulin/IGF-1, TGF-beta and cGMP signaling to control development and aging. / Barna, János; Princz, Andrea; Kosztelnik, Mónika; Hargitai, Balázsázs; Takács-Vellai, K.; Vellai, T.

In: BMC Developmental Biology, 01.11.2012, p. 32.

Research output: Contribution to journalArticle

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