ZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-κB via phosphoinosotide remodeling of endosomes
Identifieur interne : 000638 ( Ncbi/Merge ); précédent : 000637; suivant : 000639ZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-κB via phosphoinosotide remodeling of endosomes
Auteurs : Caodi Fang [États-Unis] ; Thomas D. Manes [États-Unis] ; Lufang Liu [États-Unis] ; Kevin Liu [États-Unis] ; Lingfeng Qin [États-Unis] ; Guangxin Li [États-Unis] ; Zuzana Tobiasova [États-Unis] ; Nancy C. Kirkiles-Smith [États-Unis] ; Manal Patel ; Jonathan Merola [États-Unis] ; Whitney Fu [États-Unis] ; Rebecca Liu [États-Unis] ; Catherine Xie [États-Unis] ; Gregory T. Tietjen [États-Unis] ; Peter A. Nigrovic [États-Unis] ; George Tellides [États-Unis] ; Jordan S. Pober [États-Unis] ; Dan Jane-Wit [États-Unis]Source :
- Nature Communications [ 2041-1723 ] ; 2019.
Abstract
Complement promotes vascular inflammation in transplant organ rejection and connective tissue diseases. Here we identify ZFYVE21 as a complement-induced Rab5 effector that induces non-canonical NF-κB in endothelial cells (EC). In response to membrane attack complexes (MAC), ZFYVE21 is post-translationally stabilized on MAC+Rab5+ endosomes in a Rab5- and PI(3)P-dependent manner. ZFYVE21 promotes SMURF2-mediated polyubiquitinylation and proteasome-dependent degradation of endosome-associated PTEN to induce vesicular enrichment of PI(3,4,5)P3 and sequential recruitment of activated Akt and NF-κB-inducing kinase (NIK). Pharmacologic alteration of cellular phosphoinositide content with miltefosine reduces ZFYVE21 induction, EC activation, and allograft vasculopathy in a humanized mouse model. ZFYVE21 induction distinctly occurs in response to MAC and is detected in human renal and synovial tissues. Our data identifies ZFYVE21 as a Rab5 effector, defines a Rab5-ZFYVE21-SMURF2-pAkt axis by which it mediates EC activation, and demonstrates a role for this pathway in complement-mediated conditions.
Url:
DOI: 10.1038/s41467-019-10041-2
PubMed: 31113953
PubMed Central: 6529429
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000139
- to stream Pmc, to step Curation: 000139
- to stream Pmc, to step Checkpoint: 000234
Links to Exploration step
PMC:6529429Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">ZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-κB via phosphoinosotide remodeling of endosomes</title><author><name sortKey="Fang, Caodi" sort="Fang, Caodi" uniqKey="Fang C" first="Caodi" last="Fang">Caodi Fang</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Division of Cardiovascular Medicine,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Manes, Thomas D" sort="Manes, Thomas D" uniqKey="Manes T" first="Thomas D." last="Manes">Thomas D. Manes</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Immunobiology,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Liu, Lufang" sort="Liu, Lufang" uniqKey="Liu L" first="Lufang" last="Liu">Lufang Liu</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Division of Cardiovascular Medicine,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Liu, Kevin" sort="Liu, Kevin" uniqKey="Liu K" first="Kevin" last="Liu">Kevin Liu</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Division of Cardiovascular Medicine,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Qin, Lingfeng" sort="Qin, Lingfeng" uniqKey="Qin L" first="Lingfeng" last="Qin">Lingfeng Qin</name><affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Surgery,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Li, Guangxin" sort="Li, Guangxin" uniqKey="Li G" first="Guangxin" last="Li">Guangxin Li</name><affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Surgery,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Tobiasova, Zuzana" sort="Tobiasova, Zuzana" uniqKey="Tobiasova Z" first="Zuzana" last="Tobiasova">Zuzana Tobiasova</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Immunobiology,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Kirkiles Smith, Nancy C" sort="Kirkiles Smith, Nancy C" uniqKey="Kirkiles Smith N" first="Nancy C." last="Kirkiles-Smith">Nancy C. Kirkiles-Smith</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Immunobiology,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Patel, Manal" sort="Patel, Manal" uniqKey="Patel M" first="Manal" last="Patel">Manal Patel</name><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000000121885934</institution-id><institution-id institution-id-type="GRID">grid.5335.0</institution-id><institution>St. John’s College,</institution><institution>University of Cambridge,</institution></institution-wrap>Cambridge, CB2 1TP UK</nlm:aff><wicri:noCountry code="subfield">CB2 1TP UK</wicri:noCountry></affiliation></author><author><name sortKey="Merola, Jonathan" sort="Merola, Jonathan" uniqKey="Merola J" first="Jonathan" last="Merola">Jonathan Merola</name><affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Surgery,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Fu, Whitney" sort="Fu, Whitney" uniqKey="Fu W" first="Whitney" last="Fu">Whitney Fu</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Division of Cardiovascular Medicine,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Liu, Rebecca" sort="Liu, Rebecca" uniqKey="Liu R" first="Rebecca" last="Liu">Rebecca Liu</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Immunobiology,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Xie, Catherine" sort="Xie, Catherine" uniqKey="Xie C" first="Catherine" last="Xie">Catherine Xie</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Immunobiology,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Tietjen, Gregory T" sort="Tietjen, Gregory T" uniqKey="Tietjen G" first="Gregory T." last="Tietjen">Gregory T. Tietjen</name><affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Surgery,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Nigrovic, Peter A" sort="Nigrovic, Peter A" uniqKey="Nigrovic P" first="Peter A." last="Nigrovic">Peter A. Nigrovic</name><affiliation wicri:level="2"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0378 8438</institution-id><institution-id institution-id-type="GRID">grid.2515.3</institution-id><institution>Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital and Division of Immunology,</institution><institution>Boston Children’s Hospital,</institution></institution-wrap>Boston, MA 02115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Boston</wicri:cityArea></affiliation></author><author><name sortKey="Tellides, George" sort="Tellides, George" uniqKey="Tellides G" first="George" last="Tellides">George Tellides</name><affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Surgery,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Pober, Jordan S" sort="Pober, Jordan S" uniqKey="Pober J" first="Jordan S." last="Pober">Jordan S. Pober</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Immunobiology,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Jane Wit, Dan" sort="Jane Wit, Dan" uniqKey="Jane Wit D" first="Dan" last="Jane-Wit">Dan Jane-Wit</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Division of Cardiovascular Medicine,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31113953</idno><idno type="pmc">6529429</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529429</idno><idno type="RBID">PMC:6529429</idno><idno type="doi">10.1038/s41467-019-10041-2</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000139</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000139</idno><idno type="wicri:Area/Pmc/Curation">000139</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000139</idno><idno type="wicri:Area/Pmc/Checkpoint">000234</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000234</idno><idno type="wicri:Area/Ncbi/Merge">000638</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">ZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-κB via phosphoinosotide remodeling of endosomes</title><author><name sortKey="Fang, Caodi" sort="Fang, Caodi" uniqKey="Fang C" first="Caodi" last="Fang">Caodi Fang</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Division of Cardiovascular Medicine,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Manes, Thomas D" sort="Manes, Thomas D" uniqKey="Manes T" first="Thomas D." last="Manes">Thomas D. Manes</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Immunobiology,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Liu, Lufang" sort="Liu, Lufang" uniqKey="Liu L" first="Lufang" last="Liu">Lufang Liu</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Division of Cardiovascular Medicine,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Liu, Kevin" sort="Liu, Kevin" uniqKey="Liu K" first="Kevin" last="Liu">Kevin Liu</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Division of Cardiovascular Medicine,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Qin, Lingfeng" sort="Qin, Lingfeng" uniqKey="Qin L" first="Lingfeng" last="Qin">Lingfeng Qin</name><affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Surgery,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Li, Guangxin" sort="Li, Guangxin" uniqKey="Li G" first="Guangxin" last="Li">Guangxin Li</name><affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Surgery,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Tobiasova, Zuzana" sort="Tobiasova, Zuzana" uniqKey="Tobiasova Z" first="Zuzana" last="Tobiasova">Zuzana Tobiasova</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Immunobiology,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Kirkiles Smith, Nancy C" sort="Kirkiles Smith, Nancy C" uniqKey="Kirkiles Smith N" first="Nancy C." last="Kirkiles-Smith">Nancy C. Kirkiles-Smith</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Immunobiology,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Patel, Manal" sort="Patel, Manal" uniqKey="Patel M" first="Manal" last="Patel">Manal Patel</name><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000000121885934</institution-id><institution-id institution-id-type="GRID">grid.5335.0</institution-id><institution>St. John’s College,</institution><institution>University of Cambridge,</institution></institution-wrap>Cambridge, CB2 1TP UK</nlm:aff><wicri:noCountry code="subfield">CB2 1TP UK</wicri:noCountry></affiliation></author><author><name sortKey="Merola, Jonathan" sort="Merola, Jonathan" uniqKey="Merola J" first="Jonathan" last="Merola">Jonathan Merola</name><affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Surgery,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Fu, Whitney" sort="Fu, Whitney" uniqKey="Fu W" first="Whitney" last="Fu">Whitney Fu</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Division of Cardiovascular Medicine,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Liu, Rebecca" sort="Liu, Rebecca" uniqKey="Liu R" first="Rebecca" last="Liu">Rebecca Liu</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Immunobiology,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Xie, Catherine" sort="Xie, Catherine" uniqKey="Xie C" first="Catherine" last="Xie">Catherine Xie</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Immunobiology,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Tietjen, Gregory T" sort="Tietjen, Gregory T" uniqKey="Tietjen G" first="Gregory T." last="Tietjen">Gregory T. Tietjen</name><affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Surgery,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Nigrovic, Peter A" sort="Nigrovic, Peter A" uniqKey="Nigrovic P" first="Peter A." last="Nigrovic">Peter A. Nigrovic</name><affiliation wicri:level="2"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0378 8438</institution-id><institution-id institution-id-type="GRID">grid.2515.3</institution-id><institution>Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital and Division of Immunology,</institution><institution>Boston Children’s Hospital,</institution></institution-wrap>Boston, MA 02115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Boston</wicri:cityArea></affiliation></author><author><name sortKey="Tellides, George" sort="Tellides, George" uniqKey="Tellides G" first="George" last="Tellides">George Tellides</name><affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Surgery,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Pober, Jordan S" sort="Pober, Jordan S" uniqKey="Pober J" first="Jordan S." last="Pober">Jordan S. Pober</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Immunobiology,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Jane Wit, Dan" sort="Jane Wit, Dan" uniqKey="Jane Wit D" first="Dan" last="Jane-Wit">Dan Jane-Wit</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Division of Cardiovascular Medicine,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>New Haven</wicri:cityArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Complement promotes vascular inflammation in transplant organ rejection and connective tissue diseases. Here we identify ZFYVE21 as a complement-induced Rab5 effector that induces non-canonical NF-κB in endothelial cells (EC). In response to membrane attack complexes (MAC), ZFYVE21 is post-translationally stabilized on MAC+Rab5+ endosomes in a Rab5- and PI(3)P-dependent manner. ZFYVE21 promotes SMURF2-mediated polyubiquitinylation and proteasome-dependent degradation of endosome-associated PTEN to induce vesicular enrichment of PI(3,4,5)P3 and sequential recruitment of activated Akt and NF-κB-inducing kinase (NIK). Pharmacologic alteration of cellular phosphoinositide content with miltefosine reduces ZFYVE21 induction, EC activation, and allograft vasculopathy in a humanized mouse model. ZFYVE21 induction distinctly occurs in response to MAC and is detected in human renal and synovial tissues. Our data identifies ZFYVE21 as a Rab5 effector, defines a Rab5-ZFYVE21-SMURF2-pAkt axis by which it mediates EC activation, and demonstrates a role for this pathway in complement-mediated conditions.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Jane Wit, D" uniqKey="Jane Wit D">D Jane-wit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jane Wit, D" uniqKey="Jane Wit D">D Jane-wit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bayly Jones, C" uniqKey="Bayly Jones C">C Bayly-Jones</name></author><author><name sortKey="Bubeck, D" uniqKey="Bubeck D">D Bubeck</name></author><author><name sortKey="Dunstone, Ma" uniqKey="Dunstone M">MA Dunstone</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Morgan, Bp" uniqKey="Morgan B">BP Morgan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qin, L" uniqKey="Qin L">L Qin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oeckinghaus, A" uniqKey="Oeckinghaus A">A Oeckinghaus</name></author><author><name sortKey="Hayden, Ms" uniqKey="Hayden M">MS Hayden</name></author><author><name sortKey="Ghosh, S" uniqKey="Ghosh S">S Ghosh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hammerling, Bc" uniqKey="Hammerling B">BC Hammerling</name></author><author><name sortKey="Shires, Se" uniqKey="Shires S">SE Shires</name></author><author><name sortKey="Leon, Lj" uniqKey="Leon L">LJ Leon</name></author><author><name sortKey="Cortez, Mq" uniqKey="Cortez M">MQ Cortez</name></author><author><name sortKey="Gustafsson, Aringb" uniqKey="Gustafsson A">AringB Gustafsson</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Gaullier, Jm" uniqKey="Gaullier J">JM Gaullier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kutateladze, Tg" uniqKey="Kutateladze T">TG Kutateladze</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Jin, Yp" uniqKey="Jin Y">YP Jin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hickson, I" uniqKey="Hickson I">I Hickson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blondeau, F" uniqKey="Blondeau F">F. Blondeau</name></author><author><name sortKey="Laporte, J" uniqKey="Laporte J">J. Laporte</name></author><author><name sortKey="Bodin, S" uniqKey="Bodin S">S. Bodin</name></author><author><name sortKey="Superti Furga, G" uniqKey="Superti Furga G">G. Superti-Furga</name></author><author><name sortKey="Payrastre, B" uniqKey="Payrastre B">B. Payrastre</name></author><author><name sortKey="Mandel, J L" uniqKey="Mandel J">J.-L. Mandel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Balla, Tamas" uniqKey="Balla T">Tamas Balla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Idevall Hagren, O" uniqKey="Idevall Hagren O">O Idevall-Hagren</name></author><author><name sortKey="De Camilli, P" uniqKey="De Camilli P">P de Camilli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gillooly, Dj" uniqKey="Gillooly D">DJ Gillooly.</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Patki, V" uniqKey="Patki V">V Patki</name></author><author><name sortKey="Lawe, Dc" uniqKey="Lawe D">DC Lawe</name></author><author><name sortKey="Corvera, S" uniqKey="Corvera S">S Corvera</name></author><author><name sortKey="Virbasius, Jv" uniqKey="Virbasius J">JV Virbasius</name></author><author><name sortKey="Chawla, A" uniqKey="Chawla A">A Chawla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gaffney, Pr" uniqKey="Gaffney P">PR Gaffney</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klarlund, Jk" uniqKey="Klarlund J">JK Klarlund</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Varnai, P" uniqKey="Varnai P">P Varnai</name></author><author><name sortKey="Rother, Ki" uniqKey="Rother K">KI Rother</name></author><author><name sortKey="Balla, T" uniqKey="Balla T">T Balla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oatey, Pb" uniqKey="Oatey P">PB Oatey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Naguib, A" uniqKey="Naguib A">A Naguib</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maddika, S" uniqKey="Maddika S">S Maddika</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kavsak, P" uniqKey="Kavsak P">P Kavsak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blank, M" uniqKey="Blank M">M Blank</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schechner, Js" uniqKey="Schechner J">JS Schechner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stark, Ak" uniqKey="Stark A">AK Stark</name></author><author><name sortKey="Sriskantharajah, S" uniqKey="Sriskantharajah S">S Sriskantharajah</name></author><author><name sortKey="Hessel, Em" uniqKey="Hessel E">EM Hessel</name></author><author><name sortKey="Okkenhaug, K" uniqKey="Okkenhaug K">K Okkenhaug</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Uberall, F" uniqKey="Uberall F">F Uberall</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Nauser, Cl" uniqKey="Nauser C">CL Nauser</name></author><author><name sortKey="Farrar, Ca" uniqKey="Farrar C">CA Farrar</name></author><author><name sortKey="Sacks, Sh" uniqKey="Sacks S">SH Sacks</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jane Wit, D" uniqKey="Jane Wit D">D Jane-wit</name></author><author><name sortKey="Fang, C" uniqKey="Fang C">C Fang</name></author><author><name sortKey="Goldstein, Dr" uniqKey="Goldstein D">DR Goldstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maijer, Ki" uniqKey="Maijer K">KI Maijer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Salomon, Rn" uniqKey="Salomon R">RN Salomon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Normann, Sj" uniqKey="Normann S">SJ Normann</name></author><author><name sortKey="Khan, Sr" uniqKey="Khan S">SR Khan</name></author><author><name sortKey="Leelachaikul, P" uniqKey="Leelachaikul P">P Leelachaikul</name></author><author><name sortKey="Salomon, Dr" uniqKey="Salomon D">DR Salomon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rahmani, M" uniqKey="Rahmani M">M Rahmani</name></author><author><name sortKey="Cruz, Rp" uniqKey="Cruz R">RP Cruz</name></author><author><name sortKey="Granville, Dj" uniqKey="Granville D">DJ Granville</name></author><author><name sortKey="Mcmanus, Bm" uniqKey="Mcmanus B">BM McManus</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Stenmark, H" uniqKey="Stenmark H">H Stenmark</name></author><author><name sortKey="Gaetano, V" uniqKey="Gaetano V">V Gaetano</name></author><author><name sortKey="Ullrich, O" uniqKey="Ullrich O">O Ullrich</name></author><author><name sortKey="Zerial, M" uniqKey="Zerial M">M Zerial</name></author></analytic></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Nat Commun</journal-id><journal-id journal-id-type="iso-abbrev">Nat Commun</journal-id><journal-title-group><journal-title>Nature Communications</journal-title></journal-title-group><issn pub-type="epub">2041-1723</issn><publisher><publisher-name>Nature Publishing Group UK</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31113953</article-id><article-id pub-id-type="pmc">6529429</article-id><article-id pub-id-type="publisher-id">10041</article-id><article-id pub-id-type="doi">10.1038/s41467-019-10041-2</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>ZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-κB via phosphoinosotide remodeling of endosomes</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Fang</surname><given-names>Caodi</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Manes</surname><given-names>Thomas D.</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Lufang</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0003-3017-1719</contrib-id><name><surname>Liu</surname><given-names>Kevin</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Qin</surname><given-names>Lingfeng</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Guangxin</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Tobiasova</surname><given-names>Zuzana</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kirkiles-Smith</surname><given-names>Nancy C.</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-7438-2468</contrib-id><name><surname>Patel</surname><given-names>Manal</given-names></name><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Merola</surname><given-names>Jonathan</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-6935-9121</contrib-id><name><surname>Fu</surname><given-names>Whitney</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Rebecca</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Xie</surname><given-names>Catherine</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Tietjen</surname><given-names>Gregory T.</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Nigrovic</surname><given-names>Peter A.</given-names></name><xref ref-type="aff" rid="Aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Tellides</surname><given-names>George</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Pober</surname><given-names>Jordan S.</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Jane-wit</surname><given-names>Dan</given-names></name><address><email>dan.jane-wit@yale.edu</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Division of Cardiovascular Medicine,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Immunobiology,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="ISNI">0000000419368710</institution-id><institution-id institution-id-type="GRID">grid.47100.32</institution-id><institution>Department of Surgery,</institution><institution>Yale University School of Medicine,</institution></institution-wrap>New Haven, CT 06520 USA</aff><aff id="Aff4"><label>4</label><institution-wrap><institution-id institution-id-type="ISNI">0000000121885934</institution-id><institution-id institution-id-type="GRID">grid.5335.0</institution-id><institution>St. John’s College,</institution><institution>University of Cambridge,</institution></institution-wrap>Cambridge, CB2 1TP UK</aff><aff id="Aff5"><label>5</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0378 8438</institution-id><institution-id institution-id-type="GRID">grid.2515.3</institution-id><institution>Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital and Division of Immunology,</institution><institution>Boston Children’s Hospital,</institution></institution-wrap>Boston, MA 02115 USA</aff></contrib-group><pub-date pub-type="epub"><day>21</day><month>5</month><year>2019</year></pub-date><pub-date pub-type="pmc-release"><day>21</day><month>5</month><year>2019</year></pub-date><pub-date pub-type="collection"><year>2019</year></pub-date><volume>10</volume><elocation-id>2247</elocation-id><history><date date-type="received"><day>25</day><month>2</month><year>2018</year></date><date date-type="accepted"><day>9</day><month>4</month><year>2019</year></date></history><permissions><copyright-statement>© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2019</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>.</license-p></license></permissions><abstract id="Abs1"><p id="Par1">Complement promotes vascular inflammation in transplant organ rejection and connective tissue diseases. Here we identify ZFYVE21 as a complement-induced Rab5 effector that induces non-canonical NF-κB in endothelial cells (EC). In response to membrane attack complexes (MAC), ZFYVE21 is post-translationally stabilized on MAC+Rab5+ endosomes in a Rab5- and PI(3)P-dependent manner. ZFYVE21 promotes SMURF2-mediated polyubiquitinylation and proteasome-dependent degradation of endosome-associated PTEN to induce vesicular enrichment of PI(3,4,5)P3 and sequential recruitment of activated Akt and NF-κB-inducing kinase (NIK). Pharmacologic alteration of cellular phosphoinositide content with miltefosine reduces ZFYVE21 induction, EC activation, and allograft vasculopathy in a humanized mouse model. ZFYVE21 induction distinctly occurs in response to MAC and is detected in human renal and synovial tissues. Our data identifies ZFYVE21 as a Rab5 effector, defines a Rab5-ZFYVE21-SMURF2-pAkt axis by which it mediates EC activation, and demonstrates a role for this pathway in complement-mediated conditions.</p></abstract><abstract id="Abs2" abstract-type="web-summary"><p id="Par2">Complement activation contributes to vascular inflammation in the contexts of allograft rejection and connective tissue disease. Here Fang et al. identify ZFYVE21 as a novel effector of Rab5 and find it regulates pro-inflammatory NF-κB signaling in endothelial cells in response to complement activation.</p></abstract><kwd-group kwd-group-type="npg-subject"><title>Subject terms</title><kwd>Endosomes</kwd><kwd>Small GTPases</kwd><kwd>Vascular diseases</kwd><kwd>Complement cascade</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/100000050</institution-id><institution>U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)</institution></institution-wrap></funding-source><award-id>R01-HL051014</award-id><award-id>R01HL141137-01</award-id><award-id>R00HL125895</award-id><award-id>R01-HL051014</award-id><award-id>R01HL141137-01</award-id><award-id>R00HL125895</award-id><principal-award-recipient><name><surname>Manes</surname><given-names>Thomas D.</given-names></name><name><surname>Liu</surname><given-names>Lufang</given-names></name><name><surname>Pober</surname><given-names>Jordan S.</given-names></name><name><surname>Jane-wit</surname><given-names>Dan</given-names></name></principal-award-recipient></award-group></funding-group><funding-group><award-group><funding-source><institution>National Program of Sustainability II (MEYS CR, NPU II)</institution></funding-source></award-group></funding-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/100006483</institution-id><institution>AbbVie (AbbVie Inc.)</institution></institution-wrap></funding-source><award-id>YAP-005-2013</award-id><award-id>YAP-005-2013</award-id><award-id>YAP-005-2013</award-id><principal-award-recipient><name><surname>Liu</surname><given-names>Lufang</given-names></name><name><surname>Pober</surname><given-names>Jordan S.</given-names></name><name><surname>Jane-wit</surname><given-names>Dan</given-names></name></principal-award-recipient></award-group></funding-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/100006108</institution-id><institution>U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)</institution></institution-wrap></funding-source><award-id>UL1TR001863</award-id><award-id>UL1TR001863</award-id><principal-award-recipient><name><surname>Liu</surname><given-names>Lufang</given-names></name><name><surname>Jane-wit</surname><given-names>Dan</given-names></name></principal-award-recipient></award-group></funding-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/100007211</institution-id><institution>Vasculitis Foundation (Vasculitis)</institution></institution-wrap></funding-source><award-id>P30AR053495-01A1</award-id><award-id>P30AR053495-01A1</award-id><principal-award-recipient><name><surname>Liu</surname><given-names>Lufang</given-names></name><name><surname>Jane-wit</surname><given-names>Dan</given-names></name></principal-award-recipient></award-group></funding-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/100000069</institution-id><institution>U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)</institution></institution-wrap></funding-source><award-id>P30AR070253</award-id><principal-award-recipient><name><surname>Nigrovic</surname><given-names>Peter A.</given-names></name></principal-award-recipient></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2019</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list><country><li>États-Unis</li></country><region><li>Connecticut</li><li>Massachusetts</li></region></list><tree><noCountry><name sortKey="Patel, Manal" sort="Patel, Manal" uniqKey="Patel M" first="Manal" last="Patel">Manal Patel</name></noCountry><country name="États-Unis"><region name="Connecticut"><name sortKey="Fang, Caodi" sort="Fang, Caodi" uniqKey="Fang C" first="Caodi" last="Fang">Caodi Fang</name></region><name sortKey="Fu, Whitney" sort="Fu, Whitney" uniqKey="Fu W" first="Whitney" last="Fu">Whitney Fu</name><name sortKey="Jane Wit, Dan" sort="Jane Wit, Dan" uniqKey="Jane Wit D" first="Dan" last="Jane-Wit">Dan Jane-Wit</name><name sortKey="Kirkiles Smith, Nancy C" sort="Kirkiles Smith, Nancy C" uniqKey="Kirkiles Smith N" first="Nancy C." last="Kirkiles-Smith">Nancy C. Kirkiles-Smith</name><name sortKey="Li, Guangxin" sort="Li, Guangxin" uniqKey="Li G" first="Guangxin" last="Li">Guangxin Li</name><name sortKey="Liu, Kevin" sort="Liu, Kevin" uniqKey="Liu K" first="Kevin" last="Liu">Kevin Liu</name><name sortKey="Liu, Lufang" sort="Liu, Lufang" uniqKey="Liu L" first="Lufang" last="Liu">Lufang Liu</name><name sortKey="Liu, Rebecca" sort="Liu, Rebecca" uniqKey="Liu R" first="Rebecca" last="Liu">Rebecca Liu</name><name sortKey="Manes, Thomas D" sort="Manes, Thomas D" uniqKey="Manes T" first="Thomas D." last="Manes">Thomas D. Manes</name><name sortKey="Merola, Jonathan" sort="Merola, Jonathan" uniqKey="Merola J" first="Jonathan" last="Merola">Jonathan Merola</name><name sortKey="Nigrovic, Peter A" sort="Nigrovic, Peter A" uniqKey="Nigrovic P" first="Peter A." last="Nigrovic">Peter A. Nigrovic</name><name sortKey="Pober, Jordan S" sort="Pober, Jordan S" uniqKey="Pober J" first="Jordan S." last="Pober">Jordan S. Pober</name><name sortKey="Qin, Lingfeng" sort="Qin, Lingfeng" uniqKey="Qin L" first="Lingfeng" last="Qin">Lingfeng Qin</name><name sortKey="Tellides, George" sort="Tellides, George" uniqKey="Tellides G" first="George" last="Tellides">George Tellides</name><name sortKey="Tietjen, Gregory T" sort="Tietjen, Gregory T" uniqKey="Tietjen G" first="Gregory T." last="Tietjen">Gregory T. Tietjen</name><name sortKey="Tobiasova, Zuzana" sort="Tobiasova, Zuzana" uniqKey="Tobiasova Z" first="Zuzana" last="Tobiasova">Zuzana Tobiasova</name><name sortKey="Xie, Catherine" sort="Xie, Catherine" uniqKey="Xie C" first="Catherine" last="Xie">Catherine Xie</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Ncbi/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000638 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd -nk 000638 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= Ncbi
|étape= Merge
|type= RBID
|clé= PMC:6529429
|texte= ZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-κB via phosphoinosotide remodeling of endosomes
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i -Sk "pubmed:31113953" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \
| NlmPubMed2Wicri -a ChloroquineV1
| This area was generated with Dilib version V0.6.33. |  |