Temporal and Spatial Regulation of Epsin Abundance and VEGFR3 Signaling are Required for Lymphatic Valve Formation and Function
Identifieur interne : 002464 ( Main/Exploration ); précédent : 002463; suivant : 002465Temporal and Spatial Regulation of Epsin Abundance and VEGFR3 Signaling are Required for Lymphatic Valve Formation and Function
Auteurs : Xiaolei Liu [États-Unis] ; Satish Pasula [États-Unis] ; Hoogeun Song [États-Unis] ; Kandice L. Tessneer [États-Unis] ; Yunzhou Dong [États-Unis] ; Scott Hahn [États-Unis] ; Tadayuki Yago [États-Unis] ; Megan Brophy [États-Unis] ; Baojun Chang [États-Unis] ; Xiaofeng Cai [États-Unis] ; Hao Wu [États-Unis] ; John Mcmanus [États-Unis] ; Hirotake Ichise [Japon] ; Constantin Georgescu [États-Unis] ; Jonathan D. Wren [États-Unis] ; Courtney Griffin [États-Unis] ; Lijun Xia [États-Unis] ; R. Sathish Srinivasan [États-Unis] ; Hong Chen [États-Unis]Source :
- Science signaling [ 1937-9145 ] ; 2014.
Descripteurs français
- KwdFr :
- Allèles, Animaux, Cellules endothéliales (cytologie), Croisements génétiques, Cytométrie en flux, Endocytose, Facteurs temps, Femelle, Indoles (), Ligands, Lymphoedème (métabolisme), Naphtalènes (), Noeuds lymphatiques (anatomopathologie), Plasmides (métabolisme), Prolifération cellulaire, Protéines adaptatrices du transport vésiculaire (métabolisme), Protéines à fluorescence verte (), Récepteur-3 au facteur croissance endothéliale vasculaire (métabolisme), Souris, Souris de lignée C57BL, Souris knockout, Système lymphatique (métabolisme), Séparation cellulaire, Transduction du signal.
- MESH :
- anatomopathologie : Noeuds lymphatiques.
- cytologie : Cellules endothéliales.
- métabolisme : Lymphoedème, Plasmides, Protéines adaptatrices du transport vésiculaire, Récepteur-3 au facteur croissance endothéliale vasculaire, Système lymphatique.
- Allèles, Animaux, Croisements génétiques, Cytométrie en flux, Endocytose, Facteurs temps, Femelle, Indoles, Ligands, Naphtalènes, Prolifération cellulaire, Protéines à fluorescence verte, Souris, Souris de lignée C57BL, Souris knockout, Séparation cellulaire, Transduction du signal.
English descriptors
- KwdEn :
- Adaptor Proteins, Vesicular Transport (metabolism), Alleles, Animals, Cell Proliferation, Cell Separation, Crosses, Genetic, Endocytosis, Endothelial Cells (cytology), Female, Flow Cytometry, Green Fluorescent Proteins (chemistry), Indoles (chemistry), Ligands, Lymph Nodes (pathology), Lymphatic System (metabolism), Lymphedema (metabolism), Mice, Mice, Inbred C57BL, Mice, Knockout, Naphthalenes (chemistry), Plasmids (metabolism), Signal Transduction, Time Factors, Vascular Endothelial Growth Factor Receptor-3 (metabolism).
- MESH :
- chemical , chemistry : Green Fluorescent Proteins, Indoles, Naphthalenes.
- chemical , metabolism : Adaptor Proteins, Vesicular Transport, Vascular Endothelial Growth Factor Receptor-3.
- cytology : Endothelial Cells.
- metabolism : Lymphatic System, Lymphedema, Plasmids.
- pathology : Lymph Nodes.
- Alleles, Animals, Cell Proliferation, Cell Separation, Crosses, Genetic, Endocytosis, Female, Flow Cytometry, Ligands, Mice, Mice, Inbred C57BL, Mice, Knockout, Signal Transduction, Time Factors.
Abstract
Lymphatic valves prevent the backflow of the lymph fluid and ensure proper lymphatic drainage throughout the body. Local accumulation of lymphatic fluid in tissues, a condition called lymphedema, is common in individuals with malformed lymphatic valves. The vascular endothelial growth factor receptor 3 (VEGFR3) is required for the development of lymphatic vascular system. The abundance of VEGFR3 in collecting lymphatic trunks is high before valve formation and, except at valve regions, decreases after valve formation. We found that in mesenteric lymphatics, the abundance of epsin 1 and 2, which are ubiquitin-binding adaptor proteins involved in endocytosis, was low at early stages of development. After lymphatic valve formation, the initiation of steady shear flow was associated with an increase in the abundance of epsin 1 and 2 in collecting lymphatic trunks, but not in valve regions. Epsin 1 and 2 bound to VEGFR3 and mediated the internalization and degradation of VEGFR3, resulting in termination of VEGFR3 signaling. Mice with lymphatic endothelial cell-specific deficiency of epsin 1 and 2 had dilated lymphatic capillaries, abnormally high VEGFR3 abundance in collecting lymphatics, immature lymphatic valves, and defective lymph drainage. Deletion of a single
Url:
DOI: 10.1126/scisignal.2005413
PubMed: 25314967
PubMed Central: 4226761
Affiliations:
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last="Hahn">Scott Hahn</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Yago, Tadayuki" sort="Yago, Tadayuki" uniqKey="Yago T" first="Tadayuki" last="Yago">Tadayuki Yago</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Brophy, Megan" sort="Brophy, Megan" uniqKey="Brophy M" first="Megan" last="Brophy">Megan Brophy</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Chang, Baojun" sort="Chang, Baojun" uniqKey="Chang B" first="Baojun" last="Chang">Baojun Chang</name><affiliation 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Ichise</name><affiliation wicri:level="4"><nlm:aff id="A3">Laboratory of Developmental Genetics, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Developmental Genetics, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region><settlement type="city">Tokyo</settlement></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Georgescu, Constantin" sort="Georgescu, Constantin" uniqKey="Georgescu C" first="Constantin" last="Georgescu">Constantin Georgescu</name><affiliation wicri:level="1"><nlm:aff id="A4">Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research 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Wren</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A4">Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Griffin, Courtney" sort="Griffin, Courtney" uniqKey="Griffin C" first="Courtney" last="Griffin">Courtney Griffin</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A5">Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma, OK 73126, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma, OK 73126</wicri:regionArea><wicri:noRegion>OK 73126</wicri:noRegion></affiliation></author><author><name sortKey="Xia, Lijun" sort="Xia, Lijun" uniqKey="Xia L" first="Lijun" last="Xia">Lijun Xia</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Srinivasan, R Sathish" sort="Srinivasan, R Sathish" uniqKey="Srinivasan R" first="R. Sathish" last="Srinivasan">R. Sathish Srinivasan</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Hong" sort="Chen, Hong" uniqKey="Chen H" first="Hong" last="Chen">Hong Chen</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25314967</idno><idno type="pmc">4226761</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226761</idno><idno type="RBID">PMC:4226761</idno><idno type="doi">10.1126/scisignal.2005413</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">003557</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003557</idno><idno type="wicri:Area/Pmc/Curation">003556</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">003556</idno><idno type="wicri:Area/Pmc/Checkpoint">001724</idno><idno 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Abundance and VEGFR3 Signaling are Required for Lymphatic Valve Formation and Function</title><author><name sortKey="Liu, Xiaolei" sort="Liu, Xiaolei" uniqKey="Liu X" first="Xiaolei" last="Liu">Xiaolei Liu</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Pasula, Satish" sort="Pasula, Satish" uniqKey="Pasula S" first="Satish" last="Pasula">Satish Pasula</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Song, Hoogeun" sort="Song, Hoogeun" uniqKey="Song H" first="Hoogeun" last="Song">Hoogeun Song</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Tessneer, Kandice L" sort="Tessneer, Kandice L" uniqKey="Tessneer K" first="Kandice L." last="Tessneer">Kandice L. Tessneer</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Dong, Yunzhou" sort="Dong, Yunzhou" uniqKey="Dong Y" first="Yunzhou" last="Dong">Yunzhou Dong</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Hahn, Scott" sort="Hahn, Scott" uniqKey="Hahn S" first="Scott" last="Hahn">Scott Hahn</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Yago, Tadayuki" sort="Yago, Tadayuki" uniqKey="Yago T" first="Tadayuki" last="Yago">Tadayuki Yago</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Brophy, Megan" sort="Brophy, Megan" uniqKey="Brophy M" first="Megan" last="Brophy">Megan Brophy</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Chang, Baojun" sort="Chang, Baojun" uniqKey="Chang B" first="Baojun" last="Chang">Baojun Chang</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Cai, Xiaofeng" sort="Cai, Xiaofeng" uniqKey="Cai X" first="Xiaofeng" last="Cai">Xiaofeng Cai</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Hao" sort="Wu, Hao" uniqKey="Wu H" first="Hao" last="Wu">Hao Wu</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Mcmanus, John" sort="Mcmanus, John" uniqKey="Mcmanus J" first="John" last="Mcmanus">John Mcmanus</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Ichise, Hirotake" sort="Ichise, Hirotake" uniqKey="Ichise H" first="Hirotake" last="Ichise">Hirotake Ichise</name><affiliation wicri:level="4"><nlm:aff id="A3">Laboratory of Developmental Genetics, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Developmental Genetics, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region><settlement type="city">Tokyo</settlement></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Georgescu, Constantin" sort="Georgescu, Constantin" uniqKey="Georgescu C" first="Constantin" last="Georgescu">Constantin Georgescu</name><affiliation wicri:level="1"><nlm:aff id="A4">Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Wren, Jonathan D" sort="Wren, Jonathan D" uniqKey="Wren J" first="Jonathan D." last="Wren">Jonathan D. Wren</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A4">Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Griffin, Courtney" sort="Griffin, Courtney" uniqKey="Griffin C" first="Courtney" last="Griffin">Courtney Griffin</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A5">Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma, OK 73126, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma, OK 73126</wicri:regionArea><wicri:noRegion>OK 73126</wicri:noRegion></affiliation></author><author><name sortKey="Xia, Lijun" sort="Xia, Lijun" uniqKey="Xia L" first="Lijun" last="Xia">Lijun Xia</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Srinivasan, R Sathish" sort="Srinivasan, R Sathish" uniqKey="Srinivasan R" first="R. Sathish" last="Srinivasan">R. Sathish Srinivasan</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Hong" sort="Chen, Hong" uniqKey="Chen H" first="Hong" last="Chen">Hong Chen</name><affiliation wicri:level="1"><nlm:aff id="A1">Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma, OK 73104</wicri:regionArea><wicri:noRegion>OK 73104</wicri:noRegion></affiliation></author></analytic><series><title level="j">Science signaling</title><idno type="eISSN">1937-9145</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adaptor Proteins, Vesicular Transport (metabolism)</term><term>Alleles</term><term>Animals</term><term>Cell Proliferation</term><term>Cell Separation</term><term>Crosses, Genetic</term><term>Endocytosis</term><term>Endothelial Cells (cytology)</term><term>Female</term><term>Flow Cytometry</term><term>Green Fluorescent Proteins (chemistry)</term><term>Indoles (chemistry)</term><term>Ligands</term><term>Lymph Nodes (pathology)</term><term>Lymphatic System (metabolism)</term><term>Lymphedema (metabolism)</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Naphthalenes (chemistry)</term><term>Plasmids (metabolism)</term><term>Signal Transduction</term><term>Time Factors</term><term>Vascular Endothelial Growth Factor Receptor-3 (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Allèles</term><term>Animaux</term><term>Cellules endothéliales (cytologie)</term><term>Croisements génétiques</term><term>Cytométrie en flux</term><term>Endocytose</term><term>Facteurs temps</term><term>Femelle</term><term>Indoles ()</term><term>Ligands</term><term>Lymphoedème (métabolisme)</term><term>Naphtalènes ()</term><term>Noeuds lymphatiques (anatomopathologie)</term><term>Plasmides (métabolisme)</term><term>Prolifération cellulaire</term><term>Protéines adaptatrices du transport vésiculaire (métabolisme)</term><term>Protéines à fluorescence verte ()</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire (métabolisme)</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris knockout</term><term>Système lymphatique (métabolisme)</term><term>Séparation cellulaire</term><term>Transduction du signal</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Green Fluorescent Proteins</term><term>Indoles</term><term>Naphthalenes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adaptor Proteins, Vesicular Transport</term><term>Vascular Endothelial Growth Factor Receptor-3</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Noeuds lymphatiques</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Cellules endothéliales</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Endothelial Cells</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lymphatic System</term><term>Lymphedema</term><term>Plasmids</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Lymphoedème</term><term>Plasmides</term><term>Protéines adaptatrices du transport vésiculaire</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire</term><term>Système lymphatique</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lymph Nodes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Alleles</term><term>Animals</term><term>Cell Proliferation</term><term>Cell Separation</term><term>Crosses, Genetic</term><term>Endocytosis</term><term>Female</term><term>Flow Cytometry</term><term>Ligands</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Signal Transduction</term><term>Time Factors</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Allèles</term><term>Animaux</term><term>Croisements génétiques</term><term>Cytométrie en flux</term><term>Endocytose</term><term>Facteurs temps</term><term>Femelle</term><term>Indoles</term><term>Ligands</term><term>Naphtalènes</term><term>Prolifération cellulaire</term><term>Protéines à fluorescence verte</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris knockout</term><term>Séparation cellulaire</term><term>Transduction du signal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Lymphatic valves prevent the backflow of the lymph fluid and ensure proper lymphatic drainage throughout the body. Local accumulation of lymphatic fluid in tissues, a condition called lymphedema, is common in individuals with malformed lymphatic valves. The vascular endothelial growth factor receptor 3 (VEGFR3) is required for the development of lymphatic vascular system. The abundance of VEGFR3 in collecting lymphatic trunks is high before valve formation and, except at valve regions, decreases after valve formation. We found that in mesenteric lymphatics, the abundance of epsin 1 and 2, which are ubiquitin-binding adaptor proteins involved in endocytosis, was low at early stages of development. After lymphatic valve formation, the initiation of steady shear flow was associated with an increase in the abundance of epsin 1 and 2 in collecting lymphatic trunks, but not in valve regions. Epsin 1 and 2 bound to VEGFR3 and mediated the internalization and degradation of VEGFR3, resulting in termination of VEGFR3 signaling. Mice with lymphatic endothelial cell-specific deficiency of epsin 1 and 2 had dilated lymphatic capillaries, abnormally high VEGFR3 abundance in collecting lymphatics, immature lymphatic valves, and defective lymph drainage. Deletion of a single <italic>Vegfr3</italic> allele or pharmacological suppression of VEGFR3 signaling restored normal lymphatic valve development and lymph drainage in epsin-deficient mice. Our findings establish a critical role for epsins in the temporal and spatial regulation of VEGFR3 abundance and signaling in collecting lymphatic trunks during lymphatic valve formation.</p></div></front></TEI><affiliations><list><country><li>Japon</li><li>États-Unis</li></country><region><li>Région de Kantō</li></region><settlement><li>Tokyo</li></settlement><orgName><li>Université de Tokyo</li></orgName></list><tree><country name="États-Unis"><noRegion><name sortKey="Liu, Xiaolei" sort="Liu, Xiaolei" uniqKey="Liu X" first="Xiaolei" last="Liu">Xiaolei Liu</name></noRegion><name sortKey="Brophy, Megan" sort="Brophy, Megan" uniqKey="Brophy M" first="Megan" last="Brophy">Megan Brophy</name><name sortKey="Brophy, Megan" sort="Brophy, Megan" uniqKey="Brophy M" first="Megan" last="Brophy">Megan Brophy</name><name sortKey="Cai, Xiaofeng" sort="Cai, Xiaofeng" uniqKey="Cai X" first="Xiaofeng" last="Cai">Xiaofeng Cai</name><name sortKey="Chang, Baojun" sort="Chang, Baojun" uniqKey="Chang B" first="Baojun" last="Chang">Baojun Chang</name><name sortKey="Chen, Hong" sort="Chen, Hong" uniqKey="Chen H" first="Hong" last="Chen">Hong Chen</name><name sortKey="Chen, Hong" sort="Chen, Hong" uniqKey="Chen H" first="Hong" last="Chen">Hong Chen</name><name sortKey="Dong, Yunzhou" sort="Dong, Yunzhou" uniqKey="Dong Y" first="Yunzhou" last="Dong">Yunzhou Dong</name><name sortKey="Georgescu, Constantin" sort="Georgescu, Constantin" uniqKey="Georgescu C" first="Constantin" last="Georgescu">Constantin Georgescu</name><name sortKey="Griffin, Courtney" sort="Griffin, Courtney" uniqKey="Griffin C" first="Courtney" last="Griffin">Courtney Griffin</name><name sortKey="Griffin, Courtney" sort="Griffin, Courtney" uniqKey="Griffin C" first="Courtney" last="Griffin">Courtney Griffin</name><name sortKey="Hahn, Scott" sort="Hahn, Scott" uniqKey="Hahn S" first="Scott" last="Hahn">Scott Hahn</name><name sortKey="Liu, Xiaolei" sort="Liu, Xiaolei" uniqKey="Liu X" first="Xiaolei" last="Liu">Xiaolei Liu</name><name sortKey="Mcmanus, John" sort="Mcmanus, John" uniqKey="Mcmanus J" first="John" last="Mcmanus">John Mcmanus</name><name sortKey="Pasula, Satish" sort="Pasula, Satish" uniqKey="Pasula S" first="Satish" last="Pasula">Satish Pasula</name><name sortKey="Song, Hoogeun" sort="Song, Hoogeun" uniqKey="Song H" first="Hoogeun" last="Song">Hoogeun Song</name><name sortKey="Srinivasan, R Sathish" sort="Srinivasan, R Sathish" uniqKey="Srinivasan R" first="R. Sathish" last="Srinivasan">R. Sathish Srinivasan</name><name sortKey="Tessneer, Kandice L" sort="Tessneer, Kandice L" uniqKey="Tessneer K" first="Kandice L." last="Tessneer">Kandice L. Tessneer</name><name sortKey="Wren, Jonathan D" sort="Wren, Jonathan D" uniqKey="Wren J" first="Jonathan D." last="Wren">Jonathan D. Wren</name><name sortKey="Wren, Jonathan D" sort="Wren, Jonathan D" uniqKey="Wren J" first="Jonathan D." last="Wren">Jonathan D. Wren</name><name sortKey="Wu, Hao" sort="Wu, Hao" uniqKey="Wu H" first="Hao" last="Wu">Hao Wu</name><name sortKey="Xia, Lijun" sort="Xia, Lijun" uniqKey="Xia L" first="Lijun" last="Xia">Lijun Xia</name><name sortKey="Xia, Lijun" sort="Xia, Lijun" uniqKey="Xia L" first="Lijun" last="Xia">Lijun Xia</name><name sortKey="Yago, Tadayuki" sort="Yago, Tadayuki" uniqKey="Yago T" first="Tadayuki" last="Yago">Tadayuki Yago</name></country><country name="Japon"><region name="Région de Kantō"><name sortKey="Ichise, Hirotake" sort="Ichise, Hirotake" uniqKey="Ichise H" first="Hirotake" last="Ichise">Hirotake Ichise</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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