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Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment

DC FieldValueLanguage
dc.contributor.author지헌영-
dc.date.accessioned2018-08-28T17:25:16Z-
dc.date.available2018-08-28T17:25:16Z-
dc.date.issued2018-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/162582-
dc.description.abstractNo efficient treatment exists for nephrotic syndrome (NS), a frequent cause of chronic kidney disease. Here we show mutations in six different genes (MAGI2, TNS2, DLC1, CDK20, ITSN1, ITSN2) as causing NS in 17 families with partially treatment-sensitive NS (pTSNS). These proteins interact and we delineate their roles in Rho-like small GTPase (RLSG) activity, and demonstrate deficiency for mutants of pTSNS patients. We find that CDK20 regulates DLC1. Knockdown of MAGI2, DLC1, or CDK20 in cultured podocytes reduces migration rate. Treatment with dexamethasone abolishes RhoA activation by knockdown of DLC1 or CDK20 indicating that steroid treatment in patients with pTSNS and mutations in these genes is mediated by this RLSG module. Furthermore, we discover ITSN1 and ITSN2 as podocytic guanine nucleotide exchange factors for Cdc42. We generate Itsn2-L knockout mice that recapitulate the mild NS phenotype. We, thus, define a functional network of RhoA regulation, thereby revealing potential therapeutic targets.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherNature Pub. Group-
dc.relation.isPartOfNATURE COMMUNICATIONS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleMutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Pharmacology-
dc.contributor.googleauthorShazia Ashraf-
dc.contributor.googleauthorHiroki Kudo-
dc.contributor.googleauthorJia Rao-
dc.contributor.googleauthorAtsuo Kikuchi-
dc.contributor.googleauthorEugen Widmeier-
dc.contributor.googleauthorJennifer A Lawson-
dc.contributor.googleauthorWeizhen Tan-
dc.contributor.googleauthorTobias Hermle-
dc.contributor.googleauthorJillian K Warejko-
dc.contributor.googleauthorShirlee Shril-
dc.contributor.googleauthorMerlin Airik-
dc.contributor.googleauthorTilman Jobst-Schwan-
dc.contributor.googleauthorSvjetlana Lovric-
dc.contributor.googleauthorDaniela A Braun-
dc.contributor.googleauthorHeon Yung Gee-
dc.contributor.googleauthorDavid Schapiro-
dc.contributor.googleauthorAmar J Majmundar-
dc.contributor.googleauthorCarolin E Sadowski-
dc.contributor.googleauthorWerner L Pabst-
dc.contributor.googleauthorAnkana Daga-
dc.contributor.googleauthorAmelie T van der Ven-
dc.contributor.googleauthorJohanna M Schmidt-
dc.contributor.googleauthorBoon Chuan Low-
dc.contributor.googleauthorAnjali Bansal Gupta-
dc.contributor.googleauthorBrajendra K Tripathi-
dc.contributor.googleauthorJenny Wong-
dc.contributor.googleauthorKirk Campbell-
dc.contributor.googleauthorKay Metcalfe-
dc.contributor.googleauthorDenny Schanze-
dc.contributor.googleauthorTetsuya Niihori-
dc.contributor.googleauthorHiroshi Kaito-
dc.contributor.googleauthorKandai Nozu-
dc.contributor.googleauthorHiroyasu Tsukaguchi-
dc.contributor.googleauthorRyojiro Tanaka-
dc.contributor.googleauthorKiyoshi Hamahira-
dc.contributor.googleauthorYasuko Kobayashi-
dc.contributor.googleauthorTakumi Takizawa-
dc.contributor.googleauthorRyo Funayama-
dc.contributor.googleauthorKeiko Nakayama-
dc.contributor.googleauthorYoko Aoki-
dc.contributor.googleauthorNaonori Kumagai-
dc.contributor.googleauthorKazumoto Iijima-
dc.contributor.googleauthorHenry Fehrenbach-
dc.contributor.googleauthorJameela A Kari-
dc.contributor.googleauthorSherif El Desoky-
dc.contributor.googleauthorSawsan Jalalah-
dc.contributor.googleauthorRadovan Bogdanovic-
dc.contributor.googleauthorNatasa Stajic-
dc.contributor.googleauthorHildegard Zappel-
dc.contributor.googleauthorAssel Rakhmetova-
dc.contributor.googleauthorSharon-Rose Wassmer-
dc.contributor.googleauthorTherese Jungraithmayr-
dc.contributor.googleauthorJuergen Strehlau-
dc.contributor.googleauthorAravind Selvin Kumar-
dc.contributor.googleauthorArvind Bagga-
dc.contributor.googleauthorNeveen A Soliman-
dc.contributor.googleauthorShrikant M Mane-
dc.contributor.googleauthorLewis Kaufman-
dc.contributor.googleauthorDouglas R Lowy-
dc.contributor.googleauthorMohamad A Jairajpuri-
dc.contributor.googleauthorRichard P Lifton-
dc.contributor.googleauthorYork Pei-
dc.contributor.googleauthorMartin Zenker-
dc.contributor.googleauthorShigeo Kure-
dc.contributor.googleauthorFriedhelm Hildebrandt-
dc.identifier.doi10.1038/s41467-018-04193-w-
dc.contributor.localIdA03971-
dc.relation.journalcodeJ02293-
dc.identifier.eissn2041-1723-
dc.identifier.pmid29773874-
dc.contributor.alternativeNameGee, Heon Yung-
dc.contributor.affiliatedAuthorGee, Heon Yung-
dc.citation.volume9-
dc.citation.number1-
dc.citation.startPage1960-
dc.identifier.bibliographicCitationNATURE COMMUNICATIONS, Vol.9(1) : 1960, 2018-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers

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