{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:47:16Z","timestamp":1789984036816,"version":"4.0.1"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:p>\n                    Membrane-associated guanylate kinase inverted 2 (MAGI-2) is a component of the slit diaphragm (SD) of glomerular podocytes. Here, we investigated the podocyte-specific function of MAGI-2 using newly generated podocyte-specific MAGI-2\u2013knockout (MAGI-2\u2013KO) mice. Compared with podocytes from wild-type mice, podocytes from MAGI-2\u2013KO mice exhibited SD disruption, morphologic abnormalities of foot processes, and podocyte apoptosis leading to podocyte loss. These pathologic changes manifested as massive albuminuria by 8 weeks of age and glomerulosclerosis and significantly higher plasma creatinine levels at 12 weeks of age; all MAGI-2\u2013KO mice died by 20 weeks of age. Loss of MAGI-2 in podocytes associated with decreased expression and nuclear translocation of dendrin, which is also a component of the SD complex. Dendrin translocates from the SD to the nucleus of injured podocytes, promoting apoptosis. Our coimmunoprecipitation and\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    reconstitution studies showed that dendrin is phosphorylated by Fyn and dephosphorylated by PTP1B, and that Fyn-induced phosphorylation prevents Nedd4\u20132\u2013mediated ubiquitination of dendrin. Under physiologic conditions\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    , phosphorylated dendrin localized at the SDs; in the absence of MAGI-2, dephosphorylated dendrin accumulated in the nucleus. Furthermore, induction of experimental GN in rats led to the downregulation of MAGI-2 expression and the nuclear accumulation of dendrin in podocytes. In summary, MAGI-2 and Fyn protect dendrin from Nedd4\u20132\u2013mediated ubiquitination and from nuclear translocation, thereby maintaining the physiologic homeostasis of podocytes, and the lack of MAGI-2 in podocytes results in FSGS.\n                  <\/jats:p>","DOI":"10.1681\/asn.2016121356","type":"journal-article","created":{"date-parts":[[2017,5,24]],"date-time":"2017-05-24T20:20:12Z","timestamp":1495657212000},"page":"2654-2669","source":"Crossref","is-referenced-by-count":37,"title":["Glomerulosclerosis Induced by Deficiency of Membrane-Associated Guanylate Kinase Inverted 2 in Kidney Podocytes"],"prefix":"10.1681","volume":"28","author":[{"given":"Naritoshi","family":"Shirata","sequence":"first","affiliation":[{"name":"The Laboratory for Kidney Research (TMK project), Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan;"},{"name":"Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharmaceutical Corporation, Toda, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan-ichiro","family":"Ihara","sequence":"additional","affiliation":[{"name":"The Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanae","family":"Yamamoto-Nonaka","sequence":"additional","affiliation":[{"name":"The Laboratory for Kidney Research (TMK project), Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan;"},{"name":"Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuto","family":"Seki","sequence":"additional","affiliation":[{"name":"The Laboratory for Kidney Research (TMK project), Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan;"},{"name":"Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichi","family":"Makino","sequence":"additional","affiliation":[{"name":"The Laboratory for Kidney Research (TMK project), Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan;"},{"name":"Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Alejandro","family":"Oliva Trejo","sequence":"additional","affiliation":[{"name":"The Laboratory for Kidney Research (TMK project), Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Miyake","sequence":"additional","affiliation":[{"name":"The Laboratory for Kidney Research (TMK project), Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan;"},{"name":"Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Yamada","sequence":"additional","affiliation":[{"name":"The Laboratory for Kidney Research (TMK project), Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan;"},{"name":"Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk Nicholas","family":"Campbell","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiko","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"The Laboratory for Kidney Research (TMK project), Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Mori","sequence":"additional","affiliation":[{"name":"The Laboratory for Kidney Research (TMK project), Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoko","family":"Yanagita","sequence":"additional","affiliation":[{"name":"The Laboratory for Kidney Research (TMK project), Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan;"},{"name":"Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Mundel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiko","family":"Nishimori","sequence":"additional","affiliation":[{"name":"The Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiko","family":"Asanuma","sequence":"additional","affiliation":[{"name":"The Laboratory for Kidney Research (TMK project), Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan;"},{"name":"Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan;"},{"name":"Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, 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