title: A neuronal GPCR is critical for the induction of the heat shock response in the nematode C. elegans.
abstract: In the nematode Caenorhabditis elegans, the heat shock response (HSR) is regulated at the organismal level by a network of thermosensory neurons that senses elevated temperatures and activates the HSR in remote tissues. Which neuronal receptors are required for this signaling mechanism and in which neurons they function are largely unanswered questions. Here we used worms that were engineered to exhibit RNA interference hypersensitivity in neurons to screen for neuronal receptors that are required for the activation of the HSR and identified a putative G-protein coupled receptor (GPCR) as a novel key component of this mechanism. This gene, which we termed GPCR thermal receptor 1 (gtr-1), is expressed in chemosensory neurons and has no role in heat sensing but is critically required for the induction of genes that encode heat shock proteins in non-neural tissues upon exposure to heat. Surprisingly, the knock-down of gtr-1 by RNA interference protected worms expressing the Alzheimer's-disease-linked aggregative peptide Aβ3-42 from proteotoxicity but had no effect on lifespan. This study provides several novel insights: (1) it shows that chemosensory neurons play important roles in the nematode's HSR-regulating mechanism, (2) it shows that lifespan and heat stress resistance are separable, and (3) it strengthens the emerging notion that the ability to respond to heat comes at the expense of protein homeostasis (proteostasis).
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Hebrew University School of Medicine, Jerusalem 91120, Israel.
authors.forename: Moria
authors.initials: M
authors.lastname: Maman
authors.forename: Filipa
authors.initials: F
authors.lastname: Carvalhal Marques
authors.forename: Yuli
authors.initials: Y
authors.lastname: Volovik
authors.forename: Tatyana
authors.initials: T
authors.lastname: Dubnikov
authors.forename: Michal
authors.initials: M
authors.lastname: Bejerano-Sagie
authors.forename: Ehud
authors.initials: E
authors.lastname: Cohen
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001424:Bacterial Infections / Q000517:prevention & control; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D004531:Eggs; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response / Q000235:genetics / Q000502:physiology*; D006358:Hot Temperature; D009132:Muscles / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D010243:Paralysis / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism; D037121:Plant Lectins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D012726:Sexual Behavior, Animal; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology; D013697:Thermosensing / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D029742:Caenorhabditis elegans Proteins; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D037121:Plant Lectins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors; C532271:amyloid beta-protein (3-42), pyroglutamyl(3)-; C034981:tomato lectin; D049452:Green Fluorescent Proteins
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