RRC ID 11015
著者 Stenvall J, Fierro-González JC, Swoboda P, Saamarthy K, Cheng Q, Cacho-Valadez B, Arnér ES, Persson OP, Miranda-Vizuete A, Tuck S.
タイトル Selenoprotein TRXR-1 and GSR-1 are essential for removal of old cuticle during molting in Caenorhabditis elegans.
ジャーナル Proc Natl Acad Sci U S A
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.
巻・号 108(3)
ページ 1064-9
公開日 2011-1-18
DOI 10.1073/pnas.1006328108
PII 1006328108
PMID 21199936
PMC PMC3024696
MeSH Age Factors Animals Blotting, Western Caenorhabditis elegans / physiology* Disulfides / metabolism Epidermal Cells* Glutathione Reductase / metabolism* Maleimides Molting / physiology* Oxidation-Reduction Peptide Elongation Factors / genetics Peptide Elongation Factors / metabolism Selenocysteine / metabolism Selenoproteins / metabolism* Thioredoxin-Disulfide Reductase / metabolism*
IF 9.412
引用数 44
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
線虫 tm2047