title: Selenoprotein TRXR-1 and GSR-1 are essential for removal of old cuticle during molting in Caenorhabditis elegans.
abstract: Selenoproteins, in particular thioredoxin reductase, have been implicated in countering oxidative damage occurring during aging but the molecular functions of these proteins have not been extensively investigated in different animal models. Here we demonstrate that TRXR-1 thioredoxin reductase, the sole selenoprotein in Caenorhabditis elegans, does not protect against acute oxidative stress but functions instead together with GSR-1 glutathione reductase to promote the removal of old cuticle during molting. We show that the oxidation state of disulfide groups in the cuticle is tightly regulated during the molting cycle, and that when trxr-1 and gsr-1 function is reduced, disulfide groups in the cuticle remain oxidized. A selenocysteine-to-cysteine TRXR-1 mutant fails to rescue molting defects. Furthermore, worms lacking SELB-1, the C. elegans homolog of Escherichia coli SelB or mammalian EFsec, a translation elongation factor known to be specific for selenocysteine in E. coli, fail to incorporate selenocysteine, and display the same phenotype as those lacking trxr-1. Thus, TRXR-1 function in the reduction of old cuticle is strictly selenocysteine dependent in the nematode. Exogenously supplied reduced glutathione reduces disulfide groups in the cuticle and induces apolysis, the separation of old and new cuticle, strongly suggesting that molting involves the regulated reduction of cuticle components driven by TRXR-1 and GSR-1. Using dauer larvae, we demonstrate that aged worms have a decreased capacity to molt, and decreased expression of GSR-1. Together, our results establish a function for the selenoprotein TRXR-1 and GSR-1 in the removal of old cuticle from the surface of epidermal cells.
authors.affiliation: Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Jörgen
authors.initials: J
authors.lastname: Stenvall
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Fierro-González
authors.forename: Peter
authors.initials: P
authors.lastname: Swoboda
authors.forename: Karunakar
authors.initials: K
authors.lastname: Saamarthy
authors.forename: Qing
authors.initials: Q
authors.lastname: Cheng
authors.forename: Briseida
authors.initials: B
authors.lastname: Cacho-Valadez
authors.forename: Elias S J
authors.initials: ES
authors.lastname: Arnér
authors.forename: Olof P
authors.initials: OP
authors.lastname: Persson
authors.forename: Antonio
authors.initials: A
authors.lastname: Miranda-Vizuete
authors.forename: Simon
authors.initials: S
authors.lastname: Tuck
mesh_terms: D000367:Age Factors; D000818:Animals; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000502:physiology*; D004220:Disulfides / Q000378:metabolism; D000078404:Epidermal Cells; D005980:Glutathione Reductase / Q000378:metabolism*; D008301:Maleimides; D018978:Molting / Q000502:physiology*; D010084:Oxidation-Reduction; D010445:Peptide Elongation Factors / Q000235:genetics / Q000378:metabolism; D017279:Selenocysteine / Q000378:metabolism; D051140:Selenoproteins / Q000378:metabolism*; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism*
chemical_list: C504424:Alexa Fluor 488 C5-maleimide; D004220:Disulfides; D008301:Maleimides; D010445:Peptide Elongation Factors; D051140:Selenoproteins; D017279:Selenocysteine; D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase