title: Differential regulation of the heat shock factor 1 and DAF-16 by neuronal nhl-1 in the nematode C. elegans.
abstract: In the nematode Caenorhabditis elegans, insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) reduction hyperactivates the transcription factors DAF-16 and heat shock factor 1 (HSF-1), creating long-lived, stress-resistant worms that are protected from proteotoxicity. How DAF-16 executes its distinct functions in response to IIS reduction is largely obscure. Here, we report that NHL-1, a member of the TRIM-NHL protein family, acts in chemosensory neurons to promote stress resistance in distal tissues by DAF-16 activation but is dispensable for the activation of HSF-1. The expression of nhl-1 is regulated by the IIS, defining a neuronal regulatory circuit that controls the organismal stress response. The knockdown of nhl-1 protects nematodes that express the Alzheimer-disease-associated Aβ peptide from proteotoxicity but has no effect on lifespan. Our findings indicate that DAF-16- and HSF-1-regulated heat-responsive mechanisms are differentially controlled by neurons and show that one neuronal protein can be involved in the activation of different stress responses in remote tissues.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada (IMRIC), Hebrew University School of Medicine, Jerusalem 91120, Israel.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Volovik
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada (IMRIC), Hebrew University School of Medicine, Jerusalem 91120, Israel.
authors.forename: Lorna
authors.initials: L
authors.lastname: Moll
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada (IMRIC), Hebrew University School of Medicine, Jerusalem 91120, Israel; Center of Ophthalmology and Vision Sciences (COCV), Institute for Biomedical Research in Light and Image (IBILI), Faculty of Medicine, University of Coimbra, Coimbra 3000-354, Portugal.
authors.forename: Filipa Carvalhal
authors.initials: FC
authors.lastname: Marques
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada (IMRIC), Hebrew University School of Medicine, Jerusalem 91120, Israel.
authors.forename: Moria
authors.initials: M
authors.lastname: Maman
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada (IMRIC), Hebrew University School of Medicine, Jerusalem 91120, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Bejerano-Sagie
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada (IMRIC), Hebrew University School of Medicine, Jerusalem 91120, Israel. Electronic address: ehudc@ekmd.huji.ac.il.
authors.forename: Ehud
authors.initials: E
authors.lastname: Cohen
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002628:Chemoreceptor Cells / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013002:Somatomedins / Q000378:metabolism; D013312:Stress, Physiological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; C000599609:NHL-1 protein, C elegans; D009419:Nerve Tissue Proteins; D013002:Somatomedins; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C474710:heat shock factor-1, C elegans