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Secreted metalloproteases ADAMTS9 and ADAMTS20 have a non-canonical role in ciliary vesicle growth during ciliogenesis

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dc.contributor.author지헌영-
dc.date.accessioned2020-02-11T02:21:26Z-
dc.date.available2020-02-11T02:21:26Z-
dc.date.issued2019-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/174476-
dc.description.abstractAlthough hundreds of cytosolic or transmembrane molecules form the primary cilium, few secreted molecules are known to contribute to ciliogenesis. Here, homologous secreted metalloproteases ADAMTS9 and ADAMTS20 are identified as ciliogenesis regulators that act intracellularly. Secreted and furin-processed ADAMTS9 bound heparan sulfate and was internalized by LRP1, LRP2 and clathrin-mediated endocytosis to be gathered in Rab11 vesicles with a unique periciliary localization defined by super-resolution microscopy. CRISPR-Cas9 inactivation of ADAMTS9 impaired ciliogenesis in RPE-1 cells, which was restored by catalytically active ADAMTS9 or ADAMTS20 acting in trans, but not by their proteolytically inactive mutants. Their mutagenesis in mice impaired neural and yolk sac ciliogenesis, leading to morphogenetic anomalies resulting from impaired hedgehog signaling, which is transduced by primary cilia. In addition to their cognate extracellular proteolytic activity, ADAMTS9 and ADAMTS20 thus have an additional proteolytic role intracellularly, revealing an unexpected regulatory dimension in ciliogenesis.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherNature Pub. Group-
dc.relation.isPartOfNATURE COMMUNICATIONS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHADAMTS Proteins/deficiency-
dc.subject.MESHADAMTS Proteins/genetics-
dc.subject.MESHADAMTS Proteins/metabolism*-
dc.subject.MESHADAMTS9 Protein/deficiency-
dc.subject.MESHADAMTS9 Protein/genetics-
dc.subject.MESHADAMTS9 Protein/metabolism*-
dc.subject.MESHAnimals-
dc.subject.MESHCell Line-
dc.subject.MESHCilia/metabolism*-
dc.subject.MESHCilia/ultrastructure*-
dc.subject.MESHEndocytosis-
dc.subject.MESHGene Knockout Techniques-
dc.subject.MESHHumans-
dc.subject.MESHMice-
dc.subject.MESHMice, Knockout-
dc.subject.MESHMice, Transgenic-
dc.subject.MESHMicroscopy, Electron, Scanning-
dc.subject.MESHModels, Biological-
dc.subject.MESHMutation-
dc.subject.MESHNeural Tube Defects/embryology-
dc.subject.MESHNeural Tube Defects/genetics-
dc.subject.MESHNeural Tube Defects/metabolism-
dc.subject.MESHProteolysis-
dc.subject.MESHSignal Transduction-
dc.subject.MESHVersicans/genetics-
dc.subject.MESHVersicans/metabolism-
dc.subject.MESHYolk Sac/embryology-
dc.subject.MESHYolk Sac/metabolism-
dc.titleSecreted metalloproteases ADAMTS9 and ADAMTS20 have a non-canonical role in ciliary vesicle growth during ciliogenesis-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pharmacology (약리학교실)-
dc.contributor.googleauthorSumeda Nandadasa-
dc.contributor.googleauthorCaroline M. Kraft-
dc.contributor.googleauthorLauren W. Wang-
dc.contributor.googleauthorAnna O’Donnell-
dc.contributor.googleauthorRushabh Patel-
dc.contributor.googleauthorHeon Yung Gee-
dc.contributor.googleauthorKay Grobe-
dc.contributor.googleauthorTimothy C. Cox-
dc.contributor.googleauthorFriedhelm Hildebrandt-
dc.contributor.googleauthorSuneel S. Apte-
dc.identifier.doi10.1038/s41467-019-08520-7-
dc.contributor.localIdA03971-
dc.relation.journalcodeJ02293-
dc.identifier.eissn2041-1723-
dc.identifier.pmid30814516-
dc.contributor.alternativeNameGee, Heon Yung-
dc.contributor.affiliatedAuthor지헌영-
dc.citation.volume10-
dc.citation.number1-
dc.citation.startPage953-
dc.identifier.bibliographicCitationNATURE COMMUNICATIONS, Vol.10(1) : 953, 2019-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers

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