Functional characterization of thioredoxin 3 (TRX-3), a Caenorhabditis elegans intestine-specific thioredoxin

Jiménez-Hidalgo, María et al.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. © 2013 Elsevier Inc.Some strains were provided by the CGC, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440) and the Japanese National Bioresource Project of the MEXT, Japan. We thank Howard Baylis, Keith Nehrke, Bart Braeckman, and Jim McGhee for sharing worm strains and plasmids. We are grateful to María Jesús Rodriguez-Palero and Fernando Calahorro for excellent technical assistance, to Cristina Méndez-Vidal for help with qPCR, to Helen M. Crook-McMahon for help with PRDX-2 blots, and to Britta Spanier for critical reading of the manuscript. A.M.-V. was supported by the Instituto de Salud Carlos III (Projects PI050065 and PI080557, cofinanced by the Fondo Social Europeo) and Junta de Andalucía (Projects P07-CVI-02697 and P08-CVI-03629), Spain. The work in the laboratory of P.S., a member of the NordForsk Nordic C. elegans Network, was supported by a grant from the Swedish Research Council. C.L.K. was supported by the INSERM, the CNRS, and the French Ministry of Research. E.L.B. and E.A.V. were supported by the MRC. J.R.P. was supported by the Plan de Apoyo a la Investigación, Desarrollo Tecnológico e Investigación de la Universidad de Jaén (Project UJA2011/12/55). J.C. was funded by the Spanish Ministry of Science and Innovation (Grant BFU2010-21794) and the Rioja Salud Foundation. E.L. and A.G.S. were supported by grants from the Fondo de Investigaciones Sanitarias (PI080642 and PI110120) and Ramón y Cajal Program to E.L. (Spanish government).Peer Reviewe