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Transcellular chaperone signaling is an intercellular stress-response distinct from the HSF-1-mediated heat shock response.
Miles, Jay; Townend, Sarah; Milonaityte, Dovile; Smith, William; Hodge, Francesca; Westhead, David R; van Oosten-Hawle, Patricija.
Afiliación
  • Miles J; School of Molecular and Cell Biology & Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
  • Townend S; School of Molecular and Cell Biology & Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
  • Milonaityte D; School of Molecular and Cell Biology & Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
  • Smith W; School of Molecular and Cell Biology & Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
  • Hodge F; School of Molecular and Cell Biology & Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
  • Westhead DR; School of Molecular and Cell Biology & Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
  • van Oosten-Hawle P; School of Molecular and Cell Biology & Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
PLoS Biol ; 21(2): e3001605, 2023 02.
Article en En | MEDLINE | ID: mdl-36780563
Organismal proteostasis is maintained by intercellular signaling processes including cell nonautonomous stress responses such as transcellular chaperone signaling (TCS). When TCS is activated upon tissue-specific knockdown of hsp-90 in the Caenorhabditis elegans intestine, heat-inducible hsp-70 is induced in muscle cells at the permissive temperature resulting in increased heat stress resistance and lifespan extension. However, our understanding of the molecular mechanism and signaling factors mediating transcellular activation of hsp-70 expression from one tissue to another is still in its infancy. Here, we conducted a combinatorial approach using transcriptome RNA-Seq profiling and a forward genetic mutagenesis screen to elucidate how stress signaling from the intestine to the muscle is regulated. We find that the TCS-mediated "gut-to-muscle" induction of hsp-70 expression is suppressed by HSF-1 and instead relies on transcellular-X-cross-tissue (txt) genes. We identify a key role for the PDZ-domain guanylate cyclase txt-1 and the homeobox transcription factor ceh-58 as signaling hubs in the stress receiving muscle cells to initiate hsp-70 expression and facilitate TCS-mediated heat stress resistance and lifespan extension. Our results provide a new view on cell-nonautonomous regulation of "inter-tissue" stress responses in an organism that highlight a key role for the gut. Our data suggest that the HSF-1-mediated heat shock response is switched off upon TCS activation, in favor of an intercellular stress-signaling route to safeguard survival.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Caenorhabditis elegans Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: PLoS Biol Asunto de la revista: BIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Caenorhabditis elegans Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: PLoS Biol Asunto de la revista: BIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos