Format

Send to

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

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

Author information

1
Howard Hughes Medical Institute, University of California Berkeley, Berkeley, CA 94720, USA.
2
Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
3
Scripps Research Institute, La Jolla, CA 92037, USA.
4
Genentech, South San Francisco, CA 94080, USA.
5
Howard Hughes Medical Institute, University of California Berkeley, Berkeley, CA 94720, USA. dillin@berkeley.edu.

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.

PMID:
25324391
PMCID:
PMC4403873
DOI:
10.1126/science.1253168
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center