Heterotypic Signals from Neural HSF-1 Separate Thermotolerance from Longevity

Cell Rep. 2015 Aug 18;12(7):1196-1204. doi: 10.1016/j.celrep.2015.07.026. Epub 2015 Aug 6.


Integrating stress responses across tissues is essential for the survival of multicellular organisms. The metazoan nervous system can sense protein-misfolding stress arising in different subcellular compartments and initiate cytoprotective transcriptional responses in the periphery. Several subcellular compartments possess a homotypic signal whereby the respective compartment relies on a single signaling mechanism to convey information within the affected cell to the same stress-responsive pathway in peripheral tissues. In contrast, we find that the heat shock transcription factor, HSF-1, specifies its mode of transcellular protection via two distinct signaling pathways. Upon thermal stress, neural HSF-1 primes peripheral tissues through the thermosensory neural circuit to mount a heat shock response. Independent of this thermosensory circuit, neural HSF-1 activates the FOXO transcription factor, DAF-16, in the periphery and prolongs lifespan. Thus a single transcription factor can coordinate different stress response pathways to specify its mode of protection against changing environmental conditions.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Forkhead Transcription Factors / metabolism*
  • Heat-Shock Response*
  • Longevity*
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Transcription Factors
  • daf-16 protein, C elegans
  • heat shock factor-1, C elegans