Evidence for a role for the putative Drosophila hGRX1 orthologue in copper homeostasis.
Identifieur interne : 000462 ( Main/Exploration ); précédent : 000461; suivant : 000463Evidence for a role for the putative Drosophila hGRX1 orthologue in copper homeostasis.
Auteurs : Stephen W. Mercer [Australie] ; Richard Burke [Australie]Source :
- Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine [ 1572-8773 ] ; 2016.
Descripteurs français
- KwdFr :
- MESH :
- déficit : Cuivre.
- génétique : Glutarédoxines, Protéines de Drosophila.
- métabolisme : Cuivre, Drosophila melanogaster, Glutarédoxines, Protéines de Drosophila.
- Animaux, Femelle, Homéostasie, Humains, Mâle.
English descriptors
- KwdEn :
- MESH :
- chemical , deficiency : Copper.
- chemical , genetics : Drosophila Proteins, Glutaredoxins.
- chemical , metabolism : Copper, Drosophila Proteins, Glutaredoxins.
- metabolism : Drosophila melanogaster.
- Animals, Female, Homeostasis, Humans, Male.
Abstract
Glutaredoxins are a family of small molecular weight proteins that have a central role in cellular redox regulation. Human GRX1 (hGRX1) has also been shown to play an integral role in copper homeostasis by regulating the redox activity of the metalated sites of copper chaperones such as ATOX1 and SOD1, and the copper efflux proteins ATP7A and ATP7B. To further elucidate the role of hGRX1 in copper homeostasis, we examined the impact of RNA interference-mediated knockdown of CG6852, a putative Drosophila orthologue of hGRX1. CG6852 shares ~41 % amino acid identity with hGRX1 and key functional domains including the metal-binding CXXC motif are conserved between the two proteins. Knockdown of CG6852 in the adult midline caused a thoracic cleft and reduced scutellum, phenotypes that were exacerbated by additional knockdown of copper uptake transporters Ctr1A and Ctr1B. Knockdown of CG6852 in the adult eye enhanced a copper-deficiency phenotype caused by Ctr1A knockdown while ubiquitous knockdown of CG6852 resulted a mild systemic copper deficiency. Therefore we conclude that CG6852 is a putative orthologue of hGRX1 and may play an important role in Drosophila copper homeostasis.
DOI: 10.1007/s10534-016-9946-0
PubMed: 27379771
Affiliations:
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Mercer</name><affiliation wicri:level="1"><nlm:affiliation>School of Biological Sciences, Monash University, Melbourne, VIC, Australia. stephen.mercer@unimelb.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biological Sciences, Monash University, Melbourne, VIC</wicri:regionArea><wicri:noRegion>VIC</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Pathology, University of Melbourne, Melbourne, VIC, Australia. stephen.mercer@unimelb.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pathology, University of Melbourne, Melbourne, VIC</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Burke, Richard" sort="Burke, Richard" uniqKey="Burke R" first="Richard" last="Burke">Richard Burke</name><affiliation wicri:level="1"><nlm:affiliation>School of Biological Sciences, Monash University, Melbourne, VIC, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biological Sciences, Monash University, Melbourne, VIC</wicri:regionArea><wicri:noRegion>VIC</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27379771</idno><idno type="pmid">27379771</idno><idno type="doi">10.1007/s10534-016-9946-0</idno><idno type="wicri:Area/Main/Corpus">000428</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000428</idno><idno type="wicri:Area/Main/Curation">000428</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000428</idno><idno type="wicri:Area/Main/Exploration">000428</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Evidence for a role for the putative Drosophila hGRX1 orthologue in copper homeostasis.</title><author><name sortKey="Mercer, Stephen W" sort="Mercer, Stephen W" uniqKey="Mercer S" first="Stephen W" last="Mercer">Stephen W. Mercer</name><affiliation wicri:level="1"><nlm:affiliation>School of Biological Sciences, Monash University, Melbourne, VIC, Australia. stephen.mercer@unimelb.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biological Sciences, Monash University, Melbourne, VIC</wicri:regionArea><wicri:noRegion>VIC</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Pathology, University of Melbourne, Melbourne, VIC, Australia. stephen.mercer@unimelb.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pathology, University of Melbourne, Melbourne, VIC</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Burke, Richard" sort="Burke, Richard" uniqKey="Burke R" first="Richard" last="Burke">Richard Burke</name><affiliation wicri:level="1"><nlm:affiliation>School of Biological Sciences, Monash University, Melbourne, VIC, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biological Sciences, Monash University, Melbourne, VIC</wicri:regionArea><wicri:noRegion>VIC</wicri:noRegion></affiliation></author></analytic><series><title level="j">Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine</title><idno type="eISSN">1572-8773</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Copper (deficiency)</term><term>Copper (metabolism)</term><term>Drosophila Proteins (genetics)</term><term>Drosophila Proteins (metabolism)</term><term>Drosophila melanogaster (metabolism)</term><term>Female (MeSH)</term><term>Glutaredoxins (genetics)</term><term>Glutaredoxins (metabolism)</term><term>Homeostasis (MeSH)</term><term>Humans (MeSH)</term><term>Male (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term><term>Cuivre (déficit)</term><term>Cuivre (métabolisme)</term><term>Drosophila melanogaster (métabolisme)</term><term>Femelle (MeSH)</term><term>Glutarédoxines (génétique)</term><term>Glutarédoxines (métabolisme)</term><term>Homéostasie (MeSH)</term><term>Humains (MeSH)</term><term>Mâle (MeSH)</term><term>Protéines de Drosophila (génétique)</term><term>Protéines de Drosophila (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="deficiency" xml:lang="en"><term>Copper</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Drosophila Proteins</term><term>Glutaredoxins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Copper</term><term>Drosophila Proteins</term><term>Glutaredoxins</term></keywords><keywords scheme="MESH" qualifier="déficit" xml:lang="fr"><term>Cuivre</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glutarédoxines</term><term>Protéines de Drosophila</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Drosophila melanogaster</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cuivre</term><term>Drosophila melanogaster</term><term>Glutarédoxines</term><term>Protéines de Drosophila</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Female</term><term>Homeostasis</term><term>Humans</term><term>Male</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Femelle</term><term>Homéostasie</term><term>Humains</term><term>Mâle</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Glutaredoxins are a family of small molecular weight proteins that have a central role in cellular redox regulation. Human GRX1 (hGRX1) has also been shown to play an integral role in copper homeostasis by regulating the redox activity of the metalated sites of copper chaperones such as ATOX1 and SOD1, and the copper efflux proteins ATP7A and ATP7B. To further elucidate the role of hGRX1 in copper homeostasis, we examined the impact of RNA interference-mediated knockdown of CG6852, a putative Drosophila orthologue of hGRX1. CG6852 shares ~41 % amino acid identity with hGRX1 and key functional domains including the metal-binding CXXC motif are conserved between the two proteins. Knockdown of CG6852 in the adult midline caused a thoracic cleft and reduced scutellum, phenotypes that were exacerbated by additional knockdown of copper uptake transporters Ctr1A and Ctr1B. Knockdown of CG6852 in the adult eye enhanced a copper-deficiency phenotype caused by Ctr1A knockdown while ubiquitous knockdown of CG6852 resulted a mild systemic copper deficiency. Therefore we conclude that CG6852 is a putative orthologue of hGRX1 and may play an important role in Drosophila copper homeostasis.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27379771</PMID><DateCompleted><Year>2018</Year><Month>03</Month><Day>05</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>07</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1572-8773</ISSN><JournalIssue CitedMedium="Internet"><Volume>29</Volume><Issue>4</Issue><PubDate><Year>2016</Year><Month>08</Month></PubDate></JournalIssue><Title>Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine</Title><ISOAbbreviation>Biometals</ISOAbbreviation></Journal><ArticleTitle>Evidence for a role for the putative Drosophila hGRX1 orthologue in copper homeostasis.</ArticleTitle><Pagination><MedlinePgn>705-13</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s10534-016-9946-0</ELocationID><Abstract><AbstractText>Glutaredoxins are a family of small molecular weight proteins that have a central role in cellular redox regulation. Human GRX1 (hGRX1) has also been shown to play an integral role in copper homeostasis by regulating the redox activity of the metalated sites of copper chaperones such as ATOX1 and SOD1, and the copper efflux proteins ATP7A and ATP7B. To further elucidate the role of hGRX1 in copper homeostasis, we examined the impact of RNA interference-mediated knockdown of CG6852, a putative Drosophila orthologue of hGRX1. CG6852 shares ~41 % amino acid identity with hGRX1 and key functional domains including the metal-binding CXXC motif are conserved between the two proteins. Knockdown of CG6852 in the adult midline caused a thoracic cleft and reduced scutellum, phenotypes that were exacerbated by additional knockdown of copper uptake transporters Ctr1A and Ctr1B. Knockdown of CG6852 in the adult eye enhanced a copper-deficiency phenotype caused by Ctr1A knockdown while ubiquitous knockdown of CG6852 resulted a mild systemic copper deficiency. Therefore we conclude that CG6852 is a putative orthologue of hGRX1 and may play an important role in Drosophila copper homeostasis.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Mercer</LastName><ForeName>Stephen W</ForeName><Initials>SW</Initials><AffiliationInfo><Affiliation>School of Biological Sciences, Monash University, Melbourne, VIC, Australia. stephen.mercer@unimelb.edu.au.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pathology, University of Melbourne, Melbourne, VIC, Australia. stephen.mercer@unimelb.edu.au.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Burke</LastName><ForeName>Richard</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>School of Biological Sciences, Monash University, Melbourne, VIC, Australia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>07</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Biometals</MedlineTA><NlmUniqueID>9208478</NlmUniqueID><ISSNLinking>0966-0844</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D029721">Drosophila Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C516005">GLRX protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D054477">Glutaredoxins</NameOfSubstance></Chemical><Chemical><RegistryNumber>789U1901C5</RegistryNumber><NameOfSubstance UI="D003300">Copper</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003300" MajorTopicYN="N">Copper</DescriptorName><QualifierName UI="Q000172" MajorTopicYN="N">deficiency</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D029721" MajorTopicYN="N">Drosophila Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004331" MajorTopicYN="N">Drosophila melanogaster</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D054477" MajorTopicYN="N">Glutaredoxins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006706" MajorTopicYN="Y">Homeostasis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">ATP7</Keyword><Keyword MajorTopicYN="Y">CTR1</Keyword><Keyword MajorTopicYN="Y">Copper</Keyword><Keyword MajorTopicYN="Y">Drosophila</Keyword><Keyword MajorTopicYN="Y">hGRX1</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>06</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>06</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>7</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>7</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>3</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27379771</ArticleId><ArticleId IdType="doi">10.1007/s10534-016-9946-0</ArticleId><ArticleId IdType="pii">10.1007/s10534-016-9946-0</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Australie</li></country><region><li>Victoria (État)</li></region><settlement><li>Melbourne</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="Australie"><noRegion><name sortKey="Mercer, Stephen W" sort="Mercer, Stephen W" uniqKey="Mercer S" first="Stephen W" last="Mercer">Stephen W. Mercer</name></noRegion><name sortKey="Burke, Richard" sort="Burke, Richard" uniqKey="Burke R" first="Richard" last="Burke">Richard Burke</name><name sortKey="Mercer, Stephen W" sort="Mercer, Stephen W" uniqKey="Mercer S" first="Stephen W" last="Mercer">Stephen W. Mercer</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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