title: Selenoprotein T is required for pathogenic bacteria avoidance in Caenorhabditis elegans.
abstract: Selenoprotein T (SELENOT) is an endoplasmatic reticulum (ER)-associated redoxin that contains the amino acid selenocysteine (Sec, U) within a CXXU motif within a thioredoxin-like fold. Its precise function in multicellular organisms is not completely understood although it has been shown in mammals to be involved in Ca2+homeostasis, antioxidant and neuroendocrine functions. Here, we use the model organism C. elegans to address SELENOT function in a whole organism throughout its life cycle. C. elegans possess two genes encoding SELENOT protein orthologues (SELT-1.1 and SELT-1.2), which lack Sec and contain the CXXC redox motif instead. Our results show that a Sec→Cys replacement and a gene duplication were two major evolutionary events that occurred in the nematode lineage. We find that worm SELT-1.1 localizes to the ER and is expressed in different cell types, including the nervous system. In contrast, SELT-1.2 exclusively localizes in the cytoplasm of the AWB neurons. We find that selt-1.1 and selt-1.2 single mutants as well as the double mutant are viable, but the selt-1.1 mutant is compromised under rotenone-induced oxidative stress. We demonstrate that selt-1.1, but not selt-1.2, is required for avoidance to the bacterial pathogens Serratia marcescens and Pseudomonas aeruginosa. Aversion to the noxious signal 2-nonanone is also significantly impaired in selt-1.1, but not in selt-1.2 mutant animals. Our results suggest that selt-1.1 would be a redox transducer required for nociception and optimal organismal fitness. The results highlight C. elegans as a valuable model organism to study SELENOT-dependent processes.
authors.affiliation: Worm Biology Laboratory, Institut Pasteur de Montevideo, Uruguay; Cátedra de Inmunología, Departamento de Biociencias, Facultad de Química, Universidad de la República, Montevideo, Uruguay.
authors.forename: Laura
authors.initials: L
authors.lastname: Romanelli-Cedrez
authors.affiliation: Worm Biology Laboratory, Institut Pasteur de Montevideo, Uruguay.
authors.forename: Inés
authors.initials: I
authors.lastname: Carrera
authors.affiliation: Worm Biology Laboratory, Institut Pasteur de Montevideo, Uruguay.
authors.forename: Lucía
authors.initials: L
authors.lastname: Otero
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CS IC/Universidad de Sevilla, 41013 Sevilla, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Miranda-Vizuete
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America.
authors.forename: Marco
authors.initials: M
authors.lastname: Mariotti
authors.affiliation: C. elegans Behavorial Genetics Laboratory, Neuroscience Department, University of Massachusetts Medical School, Worcester, MA, United States of America.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Alkema
authors.affiliation: Worm Biology Laboratory, Institut Pasteur de Montevideo, Uruguay; Cátedra de Inmunología, Departamento de Biociencias, Facultad de Química, Universidad de la República, Montevideo, Uruguay. Electronic address: gsalin@fq.edu.uy.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Salinas
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000276:immunology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003545:Cysteine / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D020440:Gene Duplication; D007113:Immunity, Innate; D007659:Ketones / Q000008:administration & dosage; D008018:Life Cycle Stages; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D059225:Nociception; D018384:Oxidative Stress; D021381:Protein Transport; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism*; D016868:Serratia Infections / Q000276:immunology*; D012706:Serratia marcescens / Q000276:immunology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D007659:Ketones; D051140:Selenoproteins; D003545:Cysteine; C026636:2-nonanone
keywords: C. elegans; Nematode; Pathogenic bacteria avoidance; Pseudomonas aeruginosa; SelT; SelenoT; Selenocysteine; Selenoprotein T; Serratia marcescens