title: HSF-1-mediated cytoskeletal integrity determines thermotolerance and life span.
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.
authors.affiliation: Howard Hughes Medical Institute, University of California Berkeley, Berkeley, CA 94720, USA.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Baird
authors.affiliation: Howard Hughes Medical Institute, University of California Berkeley, Berkeley, CA 94720, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Douglas
authors.affiliation: Howard Hughes Medical Institute, University of California Berkeley, Berkeley, CA 94720, USA.
authors.forename: Milos S
authors.initials: MS
authors.lastname: Simic
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Grant
authors.affiliation: Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Moresco
authors.affiliation: Howard Hughes Medical Institute, University of California Berkeley, Berkeley, CA 94720, USA.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Wolff
authors.affiliation: Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Genentech, South San Francisco, CA 94080, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Manning
authors.affiliation: Howard Hughes Medical Institute, University of California Berkeley, Berkeley, CA 94720, USA. dillin@berkeley.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Dillin
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure; D018869:Heat-Shock Response / Q000235:genetics / Q000502:physiology*; D006358:Hot Temperature; D008136:Longevity; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D019209:Troponin C / Q000235:genetics / Q000494:pharmacology*
chemical_list: D000199:Actins; D029742:Caenorhabditis elegans Proteins; C000592800:PAT-10 protein, C elegans; D014157:Transcription Factors; D019209:Troponin C; C474710:heat shock factor-1, C elegans