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

BMC Dev Biol. 2012 Nov 1;12:32. doi: 10.1186/1471-213X-12-32.

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-β (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-β and cGMP neuroendocrine systems to control development and longevity in response to diverse environmental stimuli. Furthermore, HSF-1 upregulates another TGF-β 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cyclic GMP / metabolism*
  • Cytochrome P-450 Enzyme System / metabolism
  • Heat-Shock Response / genetics
  • Insulin / metabolism
  • Insulin-Like Growth Factor I / metabolism*
  • Longevity / genetics
  • RNA Interference
  • RNA, Small Interfering
  • Signal Transduction
  • Stress, Physiological
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transforming Growth Factor beta / metabolism*
  • Up-Regulation

Substances

  • Caenorhabditis elegans Proteins
  • DAF-7 protein, C elegans
  • Insulin
  • RNA, Small Interfering
  • Transcription Factors
  • Transforming Growth Factor beta
  • heat shock factor-1, C elegans
  • Insulin-Like Growth Factor I
  • Cytochrome P-450 Enzyme System
  • DAF-9 protein, C elegans
  • Cyclic GMP