title: The thioredoxin TRX-1 modulates the function of the insulin-like neuropeptide DAF-28 during dauer formation in Caenorhabditis elegans.
abstract: Thioredoxins comprise a conserved family of redox regulators involved in many biological processes, including stress resistance and aging. We report that the C. elegans thioredoxin TRX-1 acts in ASJ head sensory neurons as a novel modulator of the insulin-like neuropeptide DAF-28 during dauer formation. We show that increased formation of stress-resistant, long-lived dauer larvae in mutants for the gene encoding the insulin-like neuropeptide DAF-28 requires TRX-1 acting in ASJ neurons, upstream of the insulin-like receptor DAF-2. Genetic rescue experiments demonstrate that redox-independent functions of TRX-1 specifically in ASJ neurons are needed for the dauer formation constitutive (Daf-c) phenotype of daf-28 mutants. GFP reporters of trx-1 and daf-28 show opposing expression patterns in dauers (i.e. trx-1 is up-regulated and daf-28 is down-regulated), an effect that is not observed in growing L2/L3 larvae. In addition, functional TRX-1 is required for the down-regulation of a GFP reporter of daf-28 during dauer formation, a process that is likely subject to DAF-28-mediated feedback regulation. Our findings demonstrate that TRX-1 modulates DAF-28 signaling by contributing to the down-regulation of daf-28 expression during dauer formation. We propose that TRX-1 acts as a fluctuating neuronal signaling modulator within ASJ neurons to monitor the adjustment of neuropeptide expression, including insulin-like proteins, during dauer formation in response to adverse environmental conditions.
authors.affiliation: Department of Biosciences and Nutrition, Center for Biosciences at NOVUM, Karolinska Institute, Huddinge, Sweden.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Fierro-González
authors.forename: Astrid
authors.initials: A
authors.lastname: Cornils
authors.forename: Joy
authors.initials: J
authors.lastname: Alcedo
authors.forename: Antonio
authors.initials: A
authors.lastname: Miranda-Vizuete
authors.forename: Peter
authors.initials: P
authors.lastname: Swoboda
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004777:Environment; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D061385:Insulins; D007814:Larva / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D061385:Insulins; D009479:Neuropeptides; C508778:TRX-1 protein, C elegans; C473608:daf-28 protein, C elegans; D013879:Thioredoxins; D011972:Receptor, Insulin