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

Heterotypic Signals from Neural HSF-1 Separate Thermotolerance from Longevity.

Author information

1
Howard Hughes Medical Institute, University of California, Berkeley CA 94720, USA.
2
The Buck Institute for Research on Aging, Novato CA 94945 USA.
3
Department of Biochemistry, University of Washington, Seattle WA 98195, USA.
#
Contributed equally

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.

PMID:
26257177
PMCID:
PMC4889220
DOI:
10.1016/j.celrep.2015.07.026
[Indexed for MEDLINE]
Free PMC Article

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