Evidence for annexin A6-dependent plasma membrane remodelling of lipid domains
Identifieur interne : 002004 ( Ncbi/Merge ); précédent : 002003; suivant : 002005Evidence for annexin A6-dependent plasma membrane remodelling of lipid domains
Auteurs : Anna Alvarez-Guaita [Espagne] ; Sandra Vilà De Muga [Espagne] ; Dylan M. Owen [Australie] ; David Williamson [Australie] ; Astrid Magenau [Australie] ; Ana García-Melero [Espagne] ; Meritxell Reverter [Espagne] ; Monira Hoque [Australie] ; Rose Cairns [Australie] ; Rhea Cornely [Australie] ; Francesc Tebar [Espagne] ; Thomas Grewal [Australie] ; Katharina Gaus [Australie] ; Jesús Ayala-Sanmartín [France] ; Carlos Enrich [Espagne] ; Carles Rentero [Espagne]Source :
- British Journal of Pharmacology [ 0007-1188 ] ; 2015.
Abstract
Annexin A6 (AnxA6) is a calcium-dependent phospholipid-binding protein that can be recruited to the plasma membrane to function as a scaffolding protein to regulate signal complex formation, endo- and exocytic pathways as well as distribution of cellular cholesterol. Here, we have investigated how AnxA6 influences the membrane order.
We used Laurdan and di-4-ANEPPDHQ staining in (i) artificial membranes; (ii) live cells to investigate membrane packing and ordered lipid phases; and (iii) a super-resolution imaging (photoactivated localization microscopy, PALM) and Ripley's K second-order point pattern analysis approach to assess how AnxA6 regulates plasma membrane order domains and protein clustering.
In artificial membranes, purified AnxA6 induced a global increase in membrane order. However, confocal microscopy using di-4-ANEPPDHQ in live cells showed that cells expressing AnxA6, which reduces plasma membrane cholesterol levels and modifies the actin cytoskeleton meshwork, displayed a decrease in membrane order (∼15 and 30% in A431 and MEF cells respectively). PALM data from Lck10 and Src15 membrane raft/non-raft markers revealed that AnxA6 expression induced clustering of both raft and non-raft markers. Altered clustering of Lck10 and Src15 in cells expressing AnxA6 was also observed after cholesterol extraction with methyl-β-cyclodextrin or actin cytoskeleton disruption with latrunculin B.
AnxA6-induced plasma membrane remodelling indicated that elevated AnxA6 expression decreased membrane order through the regulation of cellular cholesterol homeostasis and the actin cytoskeleton. This study provides the first evidence from live cells that support current models of annexins as membrane organizers.
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DOI: 10.1111/bph.13022
PubMed: 25409976
PubMed Central: 4376448
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uniqKey="Alvarez Guaita A" first="Anna" last="Alvarez-Guaita">Anna Alvarez-Guaita</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona</institution><addr-line>Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Vila De Muga, Sandra" sort="Vila De Muga, Sandra" uniqKey="Vila De Muga S" first="Sandra" last="Vilà De Muga">Sandra Vilà De Muga</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona</institution><addr-line>Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Owen, Dylan M" sort="Owen, Dylan M" 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Owen</name><affiliation wicri:level="1"><nlm:aff id="au2"><institution>Center for Vascular Research, The University of New South Wales</institution><addr-line>Sydney, NSW, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sydney, NSW</wicri:regionArea><wicri:noRegion>NSW</wicri:noRegion></affiliation></author><author><name sortKey="Williamson, David" sort="Williamson, David" uniqKey="Williamson D" first="David" last="Williamson">David Williamson</name><affiliation wicri:level="1"><nlm:aff id="au2"><institution>Center for Vascular Research, The University of New South Wales</institution><addr-line>Sydney, NSW, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sydney, NSW</wicri:regionArea><wicri:noRegion>NSW</wicri:noRegion></affiliation></author><author><name sortKey="Magenau, Astrid" sort="Magenau, Astrid" uniqKey="Magenau A" first="Astrid" last="Magenau">Astrid Magenau</name><affiliation wicri:level="1"><nlm:aff id="au2"><institution>Center for Vascular Research, The University of New South Wales</institution><addr-line>Sydney, NSW, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sydney, NSW</wicri:regionArea><wicri:noRegion>NSW</wicri:noRegion></affiliation></author><author><name sortKey="Garcia Melero, Ana" sort="Garcia Melero, Ana" uniqKey="Garcia Melero A" first="Ana" last="García-Melero">Ana García-Melero</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona</institution><addr-line>Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Reverter, Meritxell" sort="Reverter, Meritxell" uniqKey="Reverter M" first="Meritxell" last="Reverter">Meritxell Reverter</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona</institution><addr-line>Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Hoque, Monira" sort="Hoque, Monira" uniqKey="Hoque M" first="Monira" last="Hoque">Monira Hoque</name><affiliation wicri:level="1"><nlm:aff id="au3"><institution>Faculty of Pharmacy, University of Sydney</institution><addr-line>Sydney, NSW, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sydney, NSW</wicri:regionArea><wicri:noRegion>NSW</wicri:noRegion></affiliation></author><author><name sortKey="Cairns, Rose" sort="Cairns, Rose" uniqKey="Cairns R" first="Rose" last="Cairns">Rose Cairns</name><affiliation wicri:level="1"><nlm:aff id="au3"><institution>Faculty of Pharmacy, University of Sydney</institution><addr-line>Sydney, NSW, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sydney, NSW</wicri:regionArea><wicri:noRegion>NSW</wicri:noRegion></affiliation></author><author><name sortKey="Cornely, Rhea" sort="Cornely, Rhea" uniqKey="Cornely R" first="Rhea" last="Cornely">Rhea Cornely</name><affiliation wicri:level="1"><nlm:aff id="au2"><institution>Center for Vascular Research, The University of New South Wales</institution><addr-line>Sydney, NSW, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sydney, NSW</wicri:regionArea><wicri:noRegion>NSW</wicri:noRegion></affiliation></author><author><name sortKey="Tebar, Francesc" sort="Tebar, Francesc" uniqKey="Tebar F" first="Francesc" last="Tebar">Francesc Tebar</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona</institution><addr-line>Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Grewal, Thomas" sort="Grewal, Thomas" uniqKey="Grewal T" first="Thomas" last="Grewal">Thomas Grewal</name><affiliation wicri:level="1"><nlm:aff id="au3"><institution>Faculty of Pharmacy, University of Sydney</institution><addr-line>Sydney, NSW, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sydney, NSW</wicri:regionArea><wicri:noRegion>NSW</wicri:noRegion></affiliation></author><author><name sortKey="Gaus, Katharina" sort="Gaus, Katharina" uniqKey="Gaus K" first="Katharina" last="Gaus">Katharina Gaus</name><affiliation wicri:level="1"><nlm:aff id="au2"><institution>Center for Vascular Research, The University of New South Wales</institution><addr-line>Sydney, NSW, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sydney, NSW</wicri:regionArea><wicri:noRegion>NSW</wicri:noRegion></affiliation></author><author><name sortKey="Ayala Sanmartin, Jesus" sort="Ayala Sanmartin, Jesus" uniqKey="Ayala Sanmartin J" first="Jesús" last="Ayala-Sanmartín">Jesús Ayala-Sanmartín</name><affiliation wicri:level="1"><nlm:aff id="au4"><institution>Centre National de la Recherche Scientifique (CNRS), École Normale Supérieure (ENS) and Université Pierre et Marie Curie (UPMC)</institution><addr-line>Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Paris</wicri:regionArea></affiliation></author><author><name sortKey="Enrich, Carlos" sort="Enrich, Carlos" uniqKey="Enrich C" first="Carlos" last="Enrich">Carlos Enrich</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona</institution><addr-line>Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Barcelona</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au5"><institution>Centre de Recerca Biomèdica CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)</institution><addr-line>Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Rentero, Carles" sort="Rentero, Carles" uniqKey="Rentero C" first="Carles" last="Rentero">Carles Rentero</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona</institution><addr-line>Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Barcelona</wicri:regionArea></affiliation></author></analytic><series><title level="j">British Journal of Pharmacology</title><idno type="ISSN">0007-1188</idno><idno type="eISSN">1476-5381</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background and Purpose</title><p>Annexin A6 (AnxA6) is a calcium-dependent phospholipid-binding protein that can be recruited to the plasma membrane to function as a scaffolding protein to regulate signal complex formation, endo- and exocytic pathways as well as distribution of cellular cholesterol. Here, we have investigated how AnxA6 influences the membrane order.</p></sec><sec><title>Experimental Approach</title><p>We used Laurdan and di-4-ANEPPDHQ staining in (i) artificial membranes; (ii) live cells to investigate membrane packing and ordered lipid phases; and (iii) a super-resolution imaging (photoactivated localization microscopy, PALM) and Ripley's K second-order point pattern analysis approach to assess how AnxA6 regulates plasma membrane order domains and protein clustering.</p></sec><sec><title>Key Results</title><p>In artificial membranes, purified AnxA6 induced a global increase in membrane order. However, confocal microscopy using di-4-ANEPPDHQ in live cells showed that cells expressing AnxA6, which reduces plasma membrane cholesterol levels and modifies the actin cytoskeleton meshwork, displayed a decrease in membrane order (∼15 and 30% in A431 and MEF cells respectively). PALM data from Lck10 and Src15 membrane raft/non-raft markers revealed that AnxA6 expression induced clustering of both raft and non-raft markers. Altered clustering of Lck10 and Src15 in cells expressing AnxA6 was also observed after cholesterol extraction with methyl-β-cyclodextrin or actin cytoskeleton disruption with latrunculin B.</p></sec><sec><title>Conclusions and Implications</title><p>AnxA6-induced plasma membrane remodelling indicated that elevated AnxA6 expression decreased membrane order through the regulation of cellular cholesterol homeostasis and the actin cytoskeleton. This study provides the first evidence from live cells that support current models of annexins as membrane organizers.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Br J Pharmacol</journal-id><journal-id journal-id-type="iso-abbrev">Br. J. Pharmacol</journal-id><journal-id journal-id-type="publisher-id">bph</journal-id><journal-title-group><journal-title>British Journal of Pharmacology</journal-title></journal-title-group><issn pub-type="ppub">0007-1188</issn><issn pub-type="epub">1476-5381</issn><publisher><publisher-name>BlackWell Publishing Ltd</publisher-name><publisher-loc>Oxford, UK</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25409976</article-id><article-id pub-id-type="pmc">4376448</article-id><article-id pub-id-type="doi">10.1111/bph.13022</article-id><article-categories><subj-group subj-group-type="heading"><subject>Themed Section: Annexins Vii Programme</subject><subj-group subj-group-type="heading"><subject>Research Paper</subject></subj-group></subj-group></article-categories><title-group><article-title>Evidence for annexin A6-dependent plasma membrane remodelling of lipid domains</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Alvarez-Guaita</surname><given-names>Anna</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="author-notes" rid="fn1">*</xref></contrib><contrib contrib-type="author"><name><surname>Vilà de Muga</surname><given-names>Sandra</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="author-notes" rid="fn1">*</xref></contrib><contrib contrib-type="author"><name><surname>Owen</surname><given-names>Dylan M</given-names></name><xref ref-type="aff" rid="au2">2</xref><xref ref-type="author-notes" rid="fn2">†</xref></contrib><contrib contrib-type="author"><name><surname>Williamson</surname><given-names>David</given-names></name><xref ref-type="aff" rid="au2">2</xref><xref ref-type="author-notes" rid="fn3">‡</xref></contrib><contrib contrib-type="author"><name><surname>Magenau</surname><given-names>Astrid</given-names></name><xref ref-type="aff" rid="au2">2</xref><xref ref-type="author-notes" rid="fn4">§</xref></contrib><contrib contrib-type="author"><name><surname>García-Melero</surname><given-names>Ana</given-names></name><xref ref-type="aff" rid="au1">1</xref></contrib><contrib contrib-type="author"><name><surname>Reverter</surname><given-names>Meritxell</given-names></name><xref ref-type="aff" rid="au1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hoque</surname><given-names>Monira</given-names></name><xref ref-type="aff" rid="au3">3</xref></contrib><contrib contrib-type="author"><name><surname>Cairns</surname><given-names>Rose</given-names></name><xref ref-type="aff" rid="au3">3</xref></contrib><contrib contrib-type="author"><name><surname>Cornely</surname><given-names>Rhea</given-names></name><xref ref-type="aff" rid="au2">2</xref></contrib><contrib contrib-type="author"><name><surname>Tebar</surname><given-names>Francesc</given-names></name><xref ref-type="aff" rid="au1">1</xref></contrib><contrib contrib-type="author"><name><surname>Grewal</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="au3">3</xref></contrib><contrib contrib-type="author"><name><surname>Gaus</surname><given-names>Katharina</given-names></name><xref ref-type="aff" rid="au2">2</xref></contrib><contrib contrib-type="author"><name><surname>Ayala-Sanmartín</surname><given-names>Jesús</given-names></name><xref ref-type="aff" rid="au4">4</xref></contrib><contrib contrib-type="author"><name><surname>Enrich</surname><given-names>Carlos</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="aff" rid="au5">5</xref><xref ref-type="corresp" rid="cor1"></xref></contrib><contrib contrib-type="author"><name><surname>Rentero</surname><given-names>Carles</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="corresp" rid="cor1"></xref></contrib><aff id="au1"><label>1</label><institution>Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona</institution><addr-line>Barcelona, Spain</addr-line></aff><aff id="au2"><label>2</label><institution>Center for Vascular Research, The University of New South Wales</institution><addr-line>Sydney, NSW, Australia</addr-line></aff><aff id="au3"><label>3</label><institution>Faculty of Pharmacy, University of Sydney</institution><addr-line>Sydney, NSW, Australia</addr-line></aff><aff id="au4"><label>4</label><institution>Centre National de la Recherche Scientifique (CNRS), École Normale Supérieure (ENS) and Université Pierre et Marie Curie (UPMC)</institution><addr-line>Paris, France</addr-line></aff><aff id="au5"><label>5</label><institution>Centre de Recerca Biomèdica CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)</institution><addr-line>Barcelona, Spain</addr-line></aff></contrib-group><author-notes><corresp id="cor1"><bold>Correspondence</bold>, Carles Rentero and Carlos Enrich, Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain. E-mail: <email>carles.rentero@ub.edu</email>; <email>enrich@ub.edu</email></corresp><fn id="fn1"><label>*</label><p>Both authors contributed equally.</p></fn><fn id="fn2"><label>†</label><p>Present addresses: Department of Physics and Randall Division of Cell and Molecular Biophysics, King's College London London, WC2R 2LS, UK</p></fn><fn id="fn3"><label>‡</label><p>Faculty of Life Sciences, University of Manchester Manchester, M13 9PT, UK</p></fn><fn id="fn4"><label>§</label><p>Garvan Institute of Medical Research and Kinghorn Cancer Centre, Cancer Research Program, St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales Sydney, NSW, 2010, Australia</p></fn></author-notes><pub-date pub-type="ppub"><month>4</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>20</day><month>1</month><year>2015</year></pub-date><volume>172</volume><issue>7</issue><fpage>1677</fpage><lpage>1690</lpage><history><date date-type="received"><day>02</day><month>4</month><year>2014</year></date><date date-type="rev-recd"><day>11</day><month>11</month><year>2014</year></date><date date-type="accepted"><day>14</day><month>11</month><year>2014</year></date></history><permissions><copyright-statement>Copyright © 2015 The British Pharmacological Society</copyright-statement><copyright-year>2015</copyright-year></permissions><abstract><sec><title>Background and Purpose</title><p>Annexin A6 (AnxA6) is a calcium-dependent phospholipid-binding protein that can be recruited to the plasma membrane to function as a scaffolding protein to regulate signal complex formation, endo- and exocytic pathways as well as distribution of cellular cholesterol. Here, we have investigated how AnxA6 influences the membrane order.</p></sec><sec><title>Experimental Approach</title><p>We used Laurdan and di-4-ANEPPDHQ staining in (i) artificial membranes; (ii) live cells to investigate membrane packing and ordered lipid phases; and (iii) a super-resolution imaging (photoactivated localization microscopy, PALM) and Ripley's K second-order point pattern analysis approach to assess how AnxA6 regulates plasma membrane order domains and protein clustering.</p></sec><sec><title>Key Results</title><p>In artificial membranes, purified AnxA6 induced a global increase in membrane order. However, confocal microscopy using di-4-ANEPPDHQ in live cells showed that cells expressing AnxA6, which reduces plasma membrane cholesterol levels and modifies the actin cytoskeleton meshwork, displayed a decrease in membrane order (∼15 and 30% in A431 and MEF cells respectively). PALM data from Lck10 and Src15 membrane raft/non-raft markers revealed that AnxA6 expression induced clustering of both raft and non-raft markers. Altered clustering of Lck10 and Src15 in cells expressing AnxA6 was also observed after cholesterol extraction with methyl-β-cyclodextrin or actin cytoskeleton disruption with latrunculin B.</p></sec><sec><title>Conclusions and Implications</title><p>AnxA6-induced plasma membrane remodelling indicated that elevated AnxA6 expression decreased membrane order through the regulation of cellular cholesterol homeostasis and the actin cytoskeleton. This study provides the first evidence from live cells that support current models of annexins as membrane organizers.</p></sec></abstract></article-meta></front></pmc><affiliations><list><country><li>Australie</li><li>Espagne</li><li>France</li></country></list><tree><country name="Espagne"><noRegion><name sortKey="Alvarez Guaita, Anna" sort="Alvarez Guaita, Anna" uniqKey="Alvarez Guaita A" first="Anna" last="Alvarez-Guaita">Anna Alvarez-Guaita</name></noRegion><name sortKey="Enrich, Carlos" sort="Enrich, Carlos" uniqKey="Enrich C" first="Carlos" last="Enrich">Carlos Enrich</name><name sortKey="Enrich, Carlos" sort="Enrich, Carlos" uniqKey="Enrich C" first="Carlos" last="Enrich">Carlos Enrich</name><name sortKey="Garcia Melero, Ana" sort="Garcia Melero, Ana" uniqKey="Garcia Melero A" first="Ana" last="García-Melero">Ana García-Melero</name><name sortKey="Rentero, Carles" sort="Rentero, Carles" uniqKey="Rentero C" first="Carles" last="Rentero">Carles Rentero</name><name sortKey="Reverter, Meritxell" sort="Reverter, Meritxell" uniqKey="Reverter M" first="Meritxell" last="Reverter">Meritxell Reverter</name><name sortKey="Tebar, Francesc" sort="Tebar, Francesc" uniqKey="Tebar F" first="Francesc" last="Tebar">Francesc Tebar</name><name sortKey="Vila De Muga, Sandra" sort="Vila De Muga, Sandra" uniqKey="Vila De Muga S" first="Sandra" last="Vilà De Muga">Sandra Vilà De Muga</name></country><country name="Australie"><noRegion><name sortKey="Owen, Dylan M" sort="Owen, Dylan M" uniqKey="Owen D" first="Dylan M" last="Owen">Dylan M. Owen</name></noRegion><name sortKey="Cairns, Rose" sort="Cairns, Rose" uniqKey="Cairns R" first="Rose" last="Cairns">Rose Cairns</name><name sortKey="Cornely, Rhea" sort="Cornely, Rhea" uniqKey="Cornely R" first="Rhea" last="Cornely">Rhea Cornely</name><name sortKey="Gaus, Katharina" sort="Gaus, Katharina" uniqKey="Gaus K" first="Katharina" last="Gaus">Katharina Gaus</name><name sortKey="Grewal, Thomas" sort="Grewal, Thomas" uniqKey="Grewal T" first="Thomas" last="Grewal">Thomas Grewal</name><name sortKey="Hoque, Monira" sort="Hoque, Monira" uniqKey="Hoque M" first="Monira" last="Hoque">Monira Hoque</name><name sortKey="Magenau, Astrid" sort="Magenau, Astrid" uniqKey="Magenau A" first="Astrid" last="Magenau">Astrid Magenau</name><name sortKey="Williamson, David" sort="Williamson, David" uniqKey="Williamson D" first="David" last="Williamson">David Williamson</name></country><country name="France"><noRegion><name sortKey="Ayala Sanmartin, Jesus" sort="Ayala Sanmartin, Jesus" uniqKey="Ayala Sanmartin J" first="Jesús" last="Ayala-Sanmartín">Jesús Ayala-Sanmartín</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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