ZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-κB via phosphoinosotide remodeling of endosomes
Identifieur interne : 000269 ( Main/Exploration ); précédent : 000268; suivant : 000270ZFYVE21 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
Affiliations:
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
- to stream Ncbi, to step Merge: 000638
- to stream Ncbi, to step Curation: 000638
- to stream Ncbi, to step Checkpoint: 000638
- to stream Main, to step Merge: 000269
- to stream Main, to step Curation: 000269
Le 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><idno type="wicri:Area/Ncbi/Curation">000638</idno><idno type="wicri:Area/Ncbi/Checkpoint">000638</idno><idno type="wicri:Area/Main/Merge">000269</idno><idno type="wicri:Area/Main/Curation">000269</idno><idno type="wicri:Area/Main/Exploration">000269</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><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/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000269 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000269 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= Main
|étape= Exploration
|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/Main/Exploration/RBID.i -Sk "pubmed:31113953" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a ChloroquineV1
| This area was generated with Dilib version V0.6.33. |  |