title: Heterotypic Signals from Neural HSF-1 Separate Thermotolerance from Longevity.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, University of California, Berkeley CA 94720, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Douglas
authors.affiliation: Howard Hughes Medical Institute, University of California, Berkeley CA 94720, USA.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Baird
authors.affiliation: Howard Hughes Medical Institute, University of California, Berkeley CA 94720, USA.
authors.forename: Milos S
authors.initials: MS
authors.lastname: Simic
authors.affiliation: Howard Hughes Medical Institute, University of California, Berkeley CA 94720, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Uhlein
authors.affiliation: The Buck Institute for Research on Aging, Novato CA 94945 USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: McCormick
authors.affiliation: Howard Hughes Medical Institute, University of California, Berkeley CA 94720, USA.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Wolff
authors.affiliation: The Buck Institute for Research on Aging, Novato CA 94945 USA.|Department of Biochemistry, University of Washington, Seattle WA 98195, USA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kennedy
authors.affiliation: Howard Hughes Medical Institute, University of California, Berkeley CA 94720, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Dillin
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D018869:Heat-Shock Response; D008136:Longevity; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C474710:heat shock factor-1, C elegans