HSF-1-mediated cytoskeletal integrity determines thermotolerance and life span

Science. 2014 Oct 17;346(6207):360-3. doi: 10.1126/science.1253168.

Abstract

The conserved heat shock transcription factor-1 (HSF-1) is essential to cellular stress resistance and life-span determination. The canonical function of HSF-1 is to regulate a network of genes encoding molecular chaperones that protect proteins from damage caused by extrinsic environmental stress or intrinsic age-related deterioration. In Caenorhabditis elegans, we engineered a modified HSF-1 strain that increased stress resistance and longevity without enhanced chaperone induction. This health assurance acted through the regulation of the calcium-binding protein PAT-10. Loss of pat-10 caused a collapse of the actin cytoskeleton, stress resistance, and life span. Furthermore, overexpression of pat-10 increased actin filament stability, thermotolerance, and longevity, indicating that in addition to chaperone regulation, HSF-1 has a prominent role in cytoskeletal integrity, ensuring cellular function during stress and aging.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / pharmacology*
  • Caenorhabditis elegans Proteins / physiology*
  • Cytoskeleton / physiology*
  • Cytoskeleton / ultrastructure
  • Heat-Shock Response / genetics
  • Heat-Shock Response / physiology*
  • Hot Temperature
  • Longevity*
  • RNA Interference
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Troponin C / genetics
  • Troponin C / pharmacology*

Substances

  • Actins
  • Caenorhabditis elegans Proteins
  • PAT-10 protein, C elegans
  • Transcription Factors
  • Troponin C
  • heat shock factor-1, C elegans