Monday, October 27, 2014

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

Nathan A. Baird, Peter M. Douglas1, Milos S. Simic, Ana R. Grant, James J. Moresco, Suzanne C. Wolff, John R. Yates III, Gerard Manning, Andrew Dillin

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.

DOI

Journal: Science

No comments:

Post a Comment