Caenorhabditis elegans HSF‐1 is an essential nuclear protein that forms stress granule‐like structures following heat shock

Aging Cell

Elizabeth A. Morton¹ 

[1] Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

关键词: aging;    heat shock factor;    longevity;   

DOI  :  10.1111/acel.12024

来源: Wiley

【 摘 要 】

Summary

The heat shock transcription factor (HSF) is a conserved regulator of heat shock-inducible gene expression. Organismal roles for HSF in physiological processes such as development, aging, and immunity have been defined largely through studies of the single Caenorhabditis elegans HSF homolog, hsf-1. However, the molecular and cell biological properties of hsf-1 in C. elegans are incompletely understood. We generated animals expressing physiological levels of an HSF-1::GFP fusion protein and examined its function, localization, and regulation in vivo. HSF-1::GFP was functional, as measured by its ability to rescue phenotypes associated with two hsf-1 mutant alleles. Rescue of hsf-1 development phenotypes was abolished in a DNA-binding-deficient mutant, demonstrating that the transcriptional targets of hsf-1 are critical to its function even in the absence of stress. Under nonstress conditions, HSF-1::GFP was found primarily in the nucleus. Following heat shock, HSF-1::GFP rapidly and reversibly redistributed into dynamic, subnuclear structures that share many properties with human nuclear stress granules, including colocalization with markers of active transcription. Rapid formation of HSF-1 stress granules required HSF-1 DNA-binding activity, and the threshold for stress granule formation was altered by growth temperature. HSF-1 stress granule formation was not induced by inhibition of IGF signaling, a pathway previously suggested to function upstream of hsf-1. Our findings suggest that development, stress, and aging pathways may regulate HSF-1 function in distinct ways, and that HSF-1 nuclear stress granule formation is an evolutionarily conserved aspect of HSF-1 regulation in vivo.

【 授权许可】

Unknown   
© 2012 The Authors Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland