{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:32:38Z","timestamp":1792679558995,"version":"4.5.0"},"reference-count":28,"publisher":"National Academy of Sciences","issue":"38","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,9,19]]},"abstract":"<jats:p>\u03b2-Arrestins mediate internalization of plasma membrane receptors. Nephrin, a structural component of the glomerular slit diaphragm, is a single transmembrane spanning receptor and belongs to the family of adhesion molecules. Its mutation causes a hereditary nephrotic syndrome. We report the previously undescribed interaction of \u03b2-arrestin2 with the nephrin C terminus. The phosphorylation status of nephrin Y1193 regulates inversely the binding of \u03b2-arrestin2 and podocin. The Src-family member Yes, known to enhance podocin\u2013nephrin interaction by nephrin phosphorylation, diminishes \u03b2-arrestin2\u2013nephrin interaction. \u03b2-Arrestin2 induces nephrin endocytosis and attenuates nephrin signaling. This finding suggests that nephrin Y1193 serves as a molecular switch that determines the integrity of the slit diaphragm by functional competition between \u03b2-arrestin2 and podocin. This concept offers a molecular pathomechanism of slit diaphragm distortion and opens therapeutic avenues for glomerular diseases.<\/jats:p>","DOI":"10.1073\/pnas.0602587103","type":"journal-article","created":{"date-parts":[[2006,9,12]],"date-time":"2006-09-12T22:25:03Z","timestamp":1158099903000},"page":"14110-14115","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":100,"title":["\u03b2-Arrestin2 mediates nephrin endocytosis and impairs slit diaphragm integrity"],"prefix":"10.1073","volume":"103","author":[{"given":"Ivo","family":"Quack","sequence":"first","affiliation":[{"name":"*Department of Nephrology, Marienhospital Herne, Hospital of the University of Bochum, D-44625 Herne, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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