Heterotypic Signals from Neural HSF-1 Separate Thermotolerance from Longevity

Peter M. Douglas, Nathan A. Baird, Milos S. Simic, Sarah Uhlein, Mark A. McCormick, Suzanne C. Wolff, Brian K. Kennedy, Andrew Dillin

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1196-1204
Number of pages9
JournalCell Reports
Issue number7
StatePublished - Aug 18 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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