Grxcr1 Promotes Hair Bundle Development by Destabilizing the Physical Interaction between Harmonin and Sans Usher Syndrome Proteins.
Identifieur interne : 000255 ( Main/Exploration ); précédent : 000254; suivant : 000256Grxcr1 Promotes Hair Bundle Development by Destabilizing the Physical Interaction between Harmonin and Sans Usher Syndrome Proteins.
Auteurs : Bernardo Blanco-Sánchez [États-Unis] ; Aurélie Clément [États-Unis] ; Javier Fierro [États-Unis] ; Sarah Stednitz [États-Unis] ; Jennifer B. Phillips [États-Unis] ; Jeremy Wegner [États-Unis] ; Jennifer M. Panlilio [États-Unis] ; Judy L. Peirce [États-Unis] ; Philip Washbourne [États-Unis] ; Monte Westerfield [États-Unis]Source :
- Cell reports [ 2211-1247 ] ; 2018.
Descripteurs français
- KwdFr :
- Activité motrice (MeSH), Animaux (MeSH), Appareil de Golgi (métabolisme), Cellules ciliées auditives (métabolisme), Cellules rénales canines Madin-Darby (MeSH), Chiens (MeSH), Danio zébré (métabolisme), Glutarédoxines (métabolisme), Glutathion (métabolisme), Liaison aux protéines (MeSH), Mutation (génétique), Protéines de poisson-zèbre (métabolisme), Protéines de tissu nerveux (métabolisme), Spécificité du substrat (MeSH), Stéréocils (métabolisme), Syndromes d'Usher (métabolisme), Transport des protéines (MeSH).
- MESH :
- génétique : Mutation.
- métabolisme : Appareil de Golgi, Cellules ciliées auditives, Danio zébré, Glutarédoxines, Glutathion, Protéines de poisson-zèbre, Protéines de tissu nerveux, Stéréocils, Syndromes d'Usher.
- Activité motrice, Animaux, Cellules rénales canines Madin-Darby, Chiens, Liaison aux protéines, Spécificité du substrat, Transport des protéines.
English descriptors
- KwdEn :
- Animals (MeSH), Dogs (MeSH), Glutaredoxins (metabolism), Glutathione (metabolism), Golgi Apparatus (metabolism), Hair Cells, Auditory (metabolism), Madin Darby Canine Kidney Cells (MeSH), Motor Activity (MeSH), Mutation (genetics), Nerve Tissue Proteins (metabolism), Protein Binding (MeSH), Protein Transport (MeSH), Stereocilia (metabolism), Substrate Specificity (MeSH), Usher Syndromes (metabolism), Zebrafish (metabolism), Zebrafish Proteins (metabolism).
- MESH :
- chemical , metabolism : Glutaredoxins, Glutathione, Nerve Tissue Proteins, Zebrafish Proteins.
- genetics : Mutation.
- metabolism : Golgi Apparatus, Hair Cells, Auditory, Stereocilia, Usher Syndromes, Zebrafish.
- Animals, Dogs, Madin Darby Canine Kidney Cells, Motor Activity, Protein Binding, Protein Transport, Substrate Specificity.
Abstract
Morphogenesis and mechanoelectrical transduction of the hair cell mechanoreceptor depend on the correct assembly of Usher syndrome (USH) proteins into highly organized macromolecular complexes. Defects in these proteins lead to deafness and vestibular areflexia in USH patients. Mutations in a non-USH protein, glutaredoxin domain-containing cysteine-rich 1 (GRXCR1), cause non-syndromic sensorineural deafness. To understand the deglutathionylating enzyme function of GRXCR1 in deafness, we generated two grxcr1 zebrafish mutant alleles. We found that hair bundles are thinner in homozygous grxcr1 mutants, similar to the USH1 mutants ush1c (Harmonin) and ush1ga (Sans). In vitro assays showed that glutathionylation promotes the interaction between Ush1c and Ush1ga and that Grxcr1 regulates mechanoreceptor development by preventing physical interaction between these proteins without affecting the assembly of another USH1 protein complex, the Ush1c-Cadherin23-Myosin7aa tripartite complex. By elucidating the molecular mechanism through which Grxcr1 functions, we also identify a mechanism that dynamically regulates the formation of Usher protein complexes.
DOI: 10.1016/j.celrep.2018.10.005
PubMed: 30380418
PubMed Central: PMC6284068
Affiliations:
Links toward previous steps (curation, corpus...)
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Electronic address: berde@uoneuro.uoregon.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Neuroscience, University of Oregon, Eugene, OR 97403</wicri:regionArea><placeName><region type="state">Oregon</region></placeName></affiliation></author><author><name sortKey="Clement, Aurelie" sort="Clement, Aurelie" uniqKey="Clement A" first="Aurélie" last="Clément">Aurélie Clément</name><affiliation wicri:level="2"><nlm:affiliation>Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Neuroscience, University of Oregon, Eugene, OR 97403</wicri:regionArea><placeName><region type="state">Oregon</region></placeName></affiliation></author><author><name sortKey="Fierro, Javier" sort="Fierro, Javier" uniqKey="Fierro J" first="Javier" last="Fierro">Javier Fierro</name><affiliation wicri:level="2"><nlm:affiliation>Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Neuroscience, University of Oregon, Eugene, OR 97403</wicri:regionArea><placeName><region type="state">Oregon</region></placeName></affiliation></author><author><name sortKey="Stednitz, Sarah" sort="Stednitz, Sarah" uniqKey="Stednitz S" first="Sarah" last="Stednitz">Sarah Stednitz</name><affiliation wicri:level="2"><nlm:affiliation>Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Neuroscience, University of Oregon, Eugene, OR 97403</wicri:regionArea><placeName><region type="state">Oregon</region></placeName></affiliation></author><author><name sortKey="Phillips, Jennifer B" sort="Phillips, Jennifer B" uniqKey="Phillips J" first="Jennifer B" last="Phillips">Jennifer B. Phillips</name><affiliation wicri:level="2"><nlm:affiliation>Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Neuroscience, University of Oregon, Eugene, OR 97403</wicri:regionArea><placeName><region type="state">Oregon</region></placeName></affiliation></author><author><name sortKey="Wegner, Jeremy" sort="Wegner, Jeremy" uniqKey="Wegner J" first="Jeremy" last="Wegner">Jeremy Wegner</name><affiliation wicri:level="2"><nlm:affiliation>Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Neuroscience, University of Oregon, Eugene, OR 97403</wicri:regionArea><placeName><region type="state">Oregon</region></placeName></affiliation></author><author><name sortKey="Panlilio, Jennifer M" sort="Panlilio, Jennifer M" uniqKey="Panlilio J" first="Jennifer M" last="Panlilio">Jennifer M. Panlilio</name><affiliation wicri:level="2"><nlm:affiliation>Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Woods Hole Oceanographic Institution, Woods Hole, MA 02543</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Peirce, Judy L" sort="Peirce, Judy L" uniqKey="Peirce J" first="Judy L" last="Peirce">Judy L. Peirce</name><affiliation wicri:level="2"><nlm:affiliation>Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Neuroscience, University of Oregon, Eugene, OR 97403</wicri:regionArea><placeName><region type="state">Oregon</region></placeName></affiliation></author><author><name sortKey="Washbourne, Philip" sort="Washbourne, Philip" uniqKey="Washbourne P" first="Philip" last="Washbourne">Philip Washbourne</name><affiliation wicri:level="2"><nlm:affiliation>Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Neuroscience, University of Oregon, Eugene, OR 97403</wicri:regionArea><placeName><region type="state">Oregon</region></placeName></affiliation></author><author><name sortKey="Westerfield, Monte" sort="Westerfield, Monte" uniqKey="Westerfield M" first="Monte" last="Westerfield">Monte Westerfield</name><affiliation wicri:level="2"><nlm:affiliation>Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA. Electronic address: monte@uoneuro.uoregon.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute of Neuroscience, University of Oregon, Eugene, OR 97403</wicri:regionArea><placeName><region type="state">Oregon</region></placeName></affiliation></author></analytic><series><title level="j">Cell reports</title><idno type="eISSN">2211-1247</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Dogs (MeSH)</term><term>Glutaredoxins (metabolism)</term><term>Glutathione (metabolism)</term><term>Golgi Apparatus (metabolism)</term><term>Hair Cells, Auditory (metabolism)</term><term>Madin Darby Canine Kidney Cells (MeSH)</term><term>Motor Activity (MeSH)</term><term>Mutation (genetics)</term><term>Nerve Tissue Proteins (metabolism)</term><term>Protein Binding (MeSH)</term><term>Protein Transport (MeSH)</term><term>Stereocilia (metabolism)</term><term>Substrate Specificity (MeSH)</term><term>Usher Syndromes (metabolism)</term><term>Zebrafish (metabolism)</term><term>Zebrafish Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activité motrice (MeSH)</term><term>Animaux (MeSH)</term><term>Appareil de Golgi (métabolisme)</term><term>Cellules ciliées auditives (métabolisme)</term><term>Cellules rénales canines Madin-Darby (MeSH)</term><term>Chiens (MeSH)</term><term>Danio zébré (métabolisme)</term><term>Glutarédoxines (métabolisme)</term><term>Glutathion (métabolisme)</term><term>Liaison aux protéines (MeSH)</term><term>Mutation (génétique)</term><term>Protéines de poisson-zèbre (métabolisme)</term><term>Protéines de tissu nerveux (métabolisme)</term><term>Spécificité du substrat (MeSH)</term><term>Stéréocils (métabolisme)</term><term>Syndromes d'Usher (métabolisme)</term><term>Transport des protéines (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Glutaredoxins</term><term>Glutathione</term><term>Nerve Tissue Proteins</term><term>Zebrafish Proteins</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Mutation</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Mutation</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Golgi Apparatus</term><term>Hair Cells, Auditory</term><term>Stereocilia</term><term>Usher Syndromes</term><term>Zebrafish</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Appareil de Golgi</term><term>Cellules ciliées auditives</term><term>Danio zébré</term><term>Glutarédoxines</term><term>Glutathion</term><term>Protéines de poisson-zèbre</term><term>Protéines de tissu nerveux</term><term>Stéréocils</term><term>Syndromes d'Usher</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Dogs</term><term>Madin Darby Canine Kidney Cells</term><term>Motor Activity</term><term>Protein Binding</term><term>Protein Transport</term><term>Substrate Specificity</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Activité motrice</term><term>Animaux</term><term>Cellules rénales canines Madin-Darby</term><term>Chiens</term><term>Liaison aux protéines</term><term>Spécificité du substrat</term><term>Transport des protéines</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Morphogenesis and mechanoelectrical transduction of the hair cell mechanoreceptor depend on the correct assembly of Usher syndrome (USH) proteins into highly organized macromolecular complexes. Defects in these proteins lead to deafness and vestibular areflexia in USH patients. Mutations in a non-USH protein, glutaredoxin domain-containing cysteine-rich 1 (GRXCR1), cause non-syndromic sensorineural deafness. To understand the deglutathionylating enzyme function of GRXCR1 in deafness, we generated two grxcr1 zebrafish mutant alleles. We found that hair bundles are thinner in homozygous grxcr1 mutants, similar to the USH1 mutants ush1c (Harmonin) and ush1ga (Sans). In vitro assays showed that glutathionylation promotes the interaction between Ush1c and Ush1ga and that Grxcr1 regulates mechanoreceptor development by preventing physical interaction between these proteins without affecting the assembly of another USH1 protein complex, the Ush1c-Cadherin23-Myosin7aa tripartite complex. By elucidating the molecular mechanism through which Grxcr1 functions, we also identify a mechanism that dynamically regulates the formation of Usher protein complexes.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30380418</PMID><DateCompleted><Year>2019</Year><Month>12</Month><Day>10</Day></DateCompleted><DateRevised><Year>2020</Year><Month>01</Month><Day>24</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">2211-1247</ISSN><JournalIssue CitedMedium="Internet"><Volume>25</Volume><Issue>5</Issue><PubDate><Year>2018</Year><Month>10</Month><Day>30</Day></PubDate></JournalIssue><Title>Cell reports</Title><ISOAbbreviation>Cell Rep</ISOAbbreviation></Journal><ArticleTitle>Grxcr1 Promotes Hair Bundle Development by Destabilizing the Physical Interaction between Harmonin and Sans Usher Syndrome Proteins.</ArticleTitle><Pagination><MedlinePgn>1281-1291.e4</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S2211-1247(18)31568-7</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.celrep.2018.10.005</ELocationID><Abstract><AbstractText>Morphogenesis and mechanoelectrical transduction of the hair cell mechanoreceptor depend on the correct assembly of Usher syndrome (USH) proteins into highly organized macromolecular complexes. Defects in these proteins lead to deafness and vestibular areflexia in USH patients. Mutations in a non-USH protein, glutaredoxin domain-containing cysteine-rich 1 (GRXCR1), cause non-syndromic sensorineural deafness. To understand the deglutathionylating enzyme function of GRXCR1 in deafness, we generated two grxcr1 zebrafish mutant alleles. We found that hair bundles are thinner in homozygous grxcr1 mutants, similar to the USH1 mutants ush1c (Harmonin) and ush1ga (Sans). In vitro assays showed that glutathionylation promotes the interaction between Ush1c and Ush1ga and that Grxcr1 regulates mechanoreceptor development by preventing physical interaction between these proteins without affecting the assembly of another USH1 protein complex, the Ush1c-Cadherin23-Myosin7aa tripartite complex. By elucidating the molecular mechanism through which Grxcr1 functions, we also identify a mechanism that dynamically regulates the formation of Usher protein complexes.</AbstractText><CopyrightInformation>Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Blanco-Sánchez</LastName><ForeName>Bernardo</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA. Electronic address: berde@uoneuro.uoregon.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Clément</LastName><ForeName>Aurélie</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fierro</LastName><ForeName>Javier</ForeName><Initials>J</Initials><Suffix>Jr</Suffix><AffiliationInfo><Affiliation>Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stednitz</LastName><ForeName>Sarah</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Phillips</LastName><ForeName>Jennifer B</ForeName><Initials>JB</Initials><AffiliationInfo><Affiliation>Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wegner</LastName><ForeName>Jeremy</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Panlilio</LastName><ForeName>Jennifer M</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Peirce</LastName><ForeName>Judy L</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Washbourne</LastName><ForeName>Philip</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Westerfield</LastName><ForeName>Monte</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA. Electronic address: monte@uoneuro.uoregon.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>P01 HD022486</GrantID><Acronym>HD</Acronym><Agency>NICHD NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 DC004186</GrantID><Acronym>DC</Acronym><Agency>NIDCD NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R24 OD011195</GrantID><Acronym>OD</Acronym><Agency>NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 HD007348</GrantID><Acronym>HD</Acronym><Agency>NICHD NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Cell Rep</MedlineTA><NlmUniqueID>101573691</NlmUniqueID></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D054477">Glutaredoxins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009419">Nerve Tissue Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C570436">Ush1c protein, zebrafish</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D029961">Zebrafish Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C000655133">grxcr1b protein, zebrafish</NameOfSubstance></Chemical><Chemical><RegistryNumber>GAN16C9B8O</RegistryNumber><NameOfSubstance UI="D005978">Glutathione</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004285" MajorTopicYN="N">Dogs</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D054477" MajorTopicYN="N">Glutaredoxins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005978" MajorTopicYN="N">Glutathione</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006056" MajorTopicYN="N">Golgi Apparatus</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006198" MajorTopicYN="N">Hair Cells, Auditory</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D061985" MajorTopicYN="N">Madin Darby Canine Kidney 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sort="Clement, Aurelie" uniqKey="Clement A" first="Aurélie" last="Clément">Aurélie Clément</name><name sortKey="Fierro, Javier" sort="Fierro, Javier" uniqKey="Fierro J" first="Javier" last="Fierro">Javier Fierro</name><name sortKey="Panlilio, Jennifer M" sort="Panlilio, Jennifer M" uniqKey="Panlilio J" first="Jennifer M" last="Panlilio">Jennifer M. Panlilio</name><name sortKey="Peirce, Judy L" sort="Peirce, Judy L" uniqKey="Peirce J" first="Judy L" last="Peirce">Judy L. Peirce</name><name sortKey="Phillips, Jennifer B" sort="Phillips, Jennifer B" uniqKey="Phillips J" first="Jennifer B" last="Phillips">Jennifer B. Phillips</name><name sortKey="Stednitz, Sarah" sort="Stednitz, Sarah" uniqKey="Stednitz S" first="Sarah" last="Stednitz">Sarah Stednitz</name><name sortKey="Washbourne, Philip" sort="Washbourne, Philip" uniqKey="Washbourne P" first="Philip" last="Washbourne">Philip Washbourne</name><name sortKey="Wegner, Jeremy" sort="Wegner, Jeremy" uniqKey="Wegner J" first="Jeremy" last="Wegner">Jeremy Wegner</name><name sortKey="Westerfield, Monte" sort="Westerfield, Monte" uniqKey="Westerfield M" first="Monte" last="Westerfield">Monte Westerfield</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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