SMF-1, SMF-2 and SMF-3 DMT1 Orthologues Regulate and Are Regulated Differentially by Manganese Levels in C. elegans
Identifieur interne : 001E88 ( Main/Exploration ); précédent : 001E87; suivant : 001E89SMF-1, SMF-2 and SMF-3 DMT1 Orthologues Regulate and Are Regulated Differentially by Manganese Levels in C. elegans
Auteurs : Catherine Au [États-Unis] ; Alexandre Benedetto [États-Unis, Royaume-Uni] ; Joel Anderson [États-Unis] ; Arnaud Labrousse [France] ; Keith Erikson [États-Unis] ; Jonathan J. Ewbank [France] ; Michael Aschner [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2009.
Abstract
Manganese (Mn) is an essential metal that can exert toxic effects at high concentrations, eventually leading to Parkinsonism. A major transporter of Mn in mammals is the divalent-metal transporter (DMT1). We characterize here DMT1-like proteins in the nematode
Url:
DOI: 10.1371/journal.pone.0007792
PubMed: 19924247
PubMed Central: 2773845
Affiliations:
- France, Royaume-Uni, États-Unis
- Angleterre, Caroline du Nord, Grand Londres, Midi-Pyrénées, Occitanie (région administrative), Provence-Alpes-Côte d'Azur, Tennessee
- Londres, Marseille, Toulouse
- University College de Londres, Université de la Méditerranée
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Le document en format XML
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xml:lang="en" level="a" type="main">SMF-1, SMF-2 and SMF-3 DMT1 Orthologues Regulate and Are Regulated Differentially by Manganese Levels in <italic>C. elegans</italic></title><author><name sortKey="Au, Catherine" sort="Au, Catherine" uniqKey="Au C" first="Catherine" last="Au">Catherine Au</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Center for Molecular Toxicology, Vanderbilt University, Nashville, Tennessee, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Molecular Toxicology, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Benedetto, Alexandre" sort="Benedetto, Alexandre" uniqKey="Benedetto A" first="Alexandre" last="Benedetto">Alexandre Benedetto</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>Children's Hospital, Vanderbilt University, Nashville, Tennessee, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Children's Hospital, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff8"><addr-line>London Centre for Nanotechnology, University College London, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>London Centre for Nanotechnology, University College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName><orgName type="university">University College de Londres</orgName></affiliation></author><author><name sortKey="Anderson, Joel" sort="Anderson, Joel" uniqKey="Anderson J" first="Joel" last="Anderson">Joel Anderson</name><affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Department of Nutrition, The University of North Carolina Greensboro, Greensboro, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Nutrition, The University of North Carolina Greensboro, Greensboro, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Labrousse, Arnaud" sort="Labrousse, Arnaud" uniqKey="Labrousse A" first="Arnaud" last="Labrousse">Arnaud Labrousse</name><affiliation wicri:level="4"><nlm:aff id="aff5"><addr-line>Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Marseille, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université de la 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Toulouse III, Toulouse, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut de Pharmacologie et de Biologie Structurale, Université Paul Sabatier Toulouse III, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Erikson, Keith" sort="Erikson, Keith" uniqKey="Erikson K" first="Keith" last="Erikson">Keith Erikson</name><affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Department of Nutrition, The University of North Carolina Greensboro, Greensboro, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Nutrition, The University of North Carolina Greensboro, Greensboro, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Ewbank, Jonathan J" sort="Ewbank, Jonathan J" uniqKey="Ewbank J" first="Jonathan J." last="Ewbank">Jonathan J. Ewbank</name><affiliation wicri:level="4"><nlm:aff id="aff5"><addr-line>Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Marseille, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université de la Méditerranée</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff6"><addr-line>U631, INSERM, Marseille, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>U631, INSERM, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>UMR6102, CNRS, Marseille, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>UMR6102, CNRS, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Aschner, Michael" sort="Aschner, Michael" uniqKey="Aschner M" first="Michael" last="Aschner">Michael Aschner</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Center for Molecular Toxicology, Vanderbilt University, Nashville, Tennessee, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Molecular Toxicology, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>Children's Hospital, Vanderbilt University, Nashville, Tennessee, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Children's Hospital, Vanderbilt University, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Manganese (Mn) is an essential metal that can exert toxic effects at high concentrations, eventually leading to Parkinsonism. A major transporter of Mn in mammals is the divalent-metal transporter (DMT1). We characterize here DMT1-like proteins in the nematode <italic>C. elegans</italic>, which regulate and are regulated by Mn and iron (Fe) content. We identified three new DMT1-like genes in <italic>C. elegans</italic>: <italic>smf-1</italic>, <italic>smf-2</italic> and <italic>smf-3</italic>. All three can functionally substitute for loss of their yeast orthologues in <italic>S. cerevisiae</italic>. In the worm, deletion of <italic>smf-1</italic> or <italic>smf-3</italic> led to an increased Mn tolerance, while loss of <italic>smf-2</italic> led to increased Mn sensitivity. <italic>smf</italic> mRNA levels measured by QRT-PCR were up-regulated upon low Mn and down-regulated upon high Mn exposures. Translational GFP-fusions revealed that SMF-1 and SMF-3 strongly localize to partially overlapping apical regions of the gut epithelium, suggesting a differential role for SMF-1 and SMF-3 in Mn nutritional intake. Conversely, SMF-2 was detected in the marginal pharyngeal epithelium, possibly involved in metal-sensing. Analysis of metal content upon Mn exposure in <italic>smf</italic> mutants revealed that SMF-3 is required for normal Mn uptake, while <italic>smf-1</italic> was dispensable. Higher <italic>smf-2</italic> mRNA levels correlated with higher Fe content, supporting a role for SMF-2 in Fe uptake. In <italic>smf-1</italic> and <italic>smf-3</italic> but not in <italic>smf-2</italic> mutants, increased Mn exposure led to decreased Fe levels, suggesting that both metals compete for transport by SMF-2. Finally, SMF-3 was post-translationally and reversibly down-regulated following Mn-exposure. In sum, we unraveled a complex interplay of transcriptional and post-translational regulations of 3 DMT1-like transporters in two adjacent tissues, which regulate metal-content in <italic>C. elegans</italic>.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Post, Je" uniqKey="Post J">JE Post</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saric, M" uniqKey="Saric M">M Saric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wedler, Fc" uniqKey="Wedler F">FC Wedler</name></author><author><name sortKey="Denman, Rb" uniqKey="Denman R">RB Denman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Addess, Kj" uniqKey="Addess K">KJ Addess</name></author><author><name sortKey="Basilion, Jp" uniqKey="Basilion J">JP Basilion</name></author><author><name sortKey="Klausner, Rd" uniqKey="Klausner R">RD Klausner</name></author><author><name 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name="États-Unis"><region name="Tennessee"><name sortKey="Au, Catherine" sort="Au, Catherine" uniqKey="Au C" first="Catherine" last="Au">Catherine Au</name></region><name sortKey="Anderson, Joel" sort="Anderson, Joel" uniqKey="Anderson J" first="Joel" last="Anderson">Joel Anderson</name><name sortKey="Aschner, Michael" sort="Aschner, Michael" uniqKey="Aschner M" first="Michael" last="Aschner">Michael Aschner</name><name sortKey="Aschner, Michael" sort="Aschner, Michael" uniqKey="Aschner M" first="Michael" last="Aschner">Michael Aschner</name><name sortKey="Aschner, Michael" sort="Aschner, Michael" uniqKey="Aschner M" first="Michael" last="Aschner">Michael Aschner</name><name sortKey="Au, Catherine" sort="Au, Catherine" uniqKey="Au C" first="Catherine" last="Au">Catherine Au</name><name sortKey="Benedetto, Alexandre" sort="Benedetto, Alexandre" uniqKey="Benedetto A" first="Alexandre" last="Benedetto">Alexandre Benedetto</name><name sortKey="Benedetto, Alexandre" sort="Benedetto, Alexandre" uniqKey="Benedetto A" first="Alexandre" last="Benedetto">Alexandre Benedetto</name><name sortKey="Erikson, Keith" sort="Erikson, Keith" uniqKey="Erikson K" first="Keith" last="Erikson">Keith Erikson</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Benedetto, Alexandre" sort="Benedetto, Alexandre" uniqKey="Benedetto A" first="Alexandre" last="Benedetto">Alexandre Benedetto</name></region></country><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Labrousse, Arnaud" sort="Labrousse, Arnaud" uniqKey="Labrousse A" first="Arnaud" last="Labrousse">Arnaud Labrousse</name></region><name sortKey="Ewbank, Jonathan J" sort="Ewbank, Jonathan J" uniqKey="Ewbank J" first="Jonathan J." last="Ewbank">Jonathan J. Ewbank</name><name sortKey="Ewbank, Jonathan J" sort="Ewbank, Jonathan J" uniqKey="Ewbank J" first="Jonathan J." last="Ewbank">Jonathan J. Ewbank</name><name sortKey="Ewbank, Jonathan J" sort="Ewbank, Jonathan J" uniqKey="Ewbank J" first="Jonathan J." last="Ewbank">Jonathan J. Ewbank</name><name sortKey="Labrousse, Arnaud" sort="Labrousse, Arnaud" uniqKey="Labrousse A" first="Arnaud" last="Labrousse">Arnaud Labrousse</name><name sortKey="Labrousse, Arnaud" sort="Labrousse, Arnaud" uniqKey="Labrousse A" first="Arnaud" last="Labrousse">Arnaud Labrousse</name><name sortKey="Labrousse, Arnaud" sort="Labrousse, Arnaud" uniqKey="Labrousse A" first="Arnaud" last="Labrousse">Arnaud Labrousse</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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