Abstract
Thioredoxins are a class of evolutionarily conserved proteins that have been demonstrated to play a key role in many cellular processes involving redox reactions. We report here the genetic and biochemical characterization of Caenorhabditis elegans TRX-3, the first metazoan thioredoxin with an intestine-specific expression pattern. By using green fluorescent protein reporters we have found that TRX-3 is expressed in both the cytoplasm and the nucleus of intestinal cells, with a prominent localization at the apical membrane. Although intestinal function, reproductive capacity, longevity, and resistance of trx-3 loss-of-function mutants to many stresses are indistinguishable from those of wild-type animals, we have observed a slight reduction in size and a minor reduction in the defecation cycle timing of trx-3 mutants. Interestingly, trx-3 is induced upon infection by Photorhabdus luminescens and Candida albicans, and TRX-3 overexpression provides a modest protection against these pathogens. Together, our data indicate that TRX-3 function in the intestine is dispensable for C. elegans development but may be important to fight specific bacterial and fungal infections.
Highlights
The thioredoxin system is one of the most important systems to maintain redox homeostasis in all eukaryotes [1]
C. elegans TRX-3 is a functional thioredoxin expressed in the intestine - The C. elegans genome encodes for nine members of the thioredoxin system with the conserved active site sequence WCGPC (Supplementary Table 3) of which only TRX-1, TRX-2, PNG-1 and DNJ-27 have been characterized to date [3, 6, 8, 10]
Consistent with this prediction, recombinant TRX-3 is devoid of enzymatic activity both in the DTT and the NADPH/thioredoxin reductase assays while native TRX-3 is fully active (Figure 1C and 1D)
Summary
The thioredoxin system is one of the most important systems to maintain redox homeostasis in all eukaryotes [1]. Thioredoxins act as general protein disulfide reductases reducing many different substrates and becoming inactive in the process by the oxidation of the two cysteine residues at the active site. The Caenorhabtidis elegans genome codes for several thioredoxin family members only a few of them have been characterized to date. TRX-2 is a mitochondrial thioredoxin of unknown function that is induced when mitochondrial unfolded protein response is activated [6]. Both TRX-1 and TRX-2 have been shown to modulate the function of CEP-1 (the worm orthologue of the tumor suppressor p53) in neuronal integrity and lifespan [7]. DNJ-27 is the worm ortholog of human ERdj which has been recently shown to mediate some pathological phenotypes of C. elegans models of human neurodegenerative diseases [10]
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