{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:46:06Z","timestamp":1789789566999,"version":"4.0.1"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>\n                    Nephrin is a key structural component of the podocyte slit diaphragm, and proper expression of nephrin on the cell surface is critical to ensure integrity of the blood filtration barrier. Maintenance of nephrin within this unique cell junction has been proposed to require dynamic phosphorylation events and endocytic recycling, although the molecular mechanisms that control this interplay are poorly understood. Here, we investigated the possibility that the phosphotyrosine adaptor protein ShcA regulates nephrin turnover. Western blotting and immunostaining analysis confirmed that ShcA is expressed in podocytes. In immunoprecipitation and pulldown assays, ShcA,\n                    <jats:italic toggle=\"yes\">via<\/jats:italic>\n                    its SH2 domain, was associated with several phosphorylated tyrosine residues on nephrin. Overexpression of ShcA promoted nephrin tyrosine phosphorylation and reduced nephrin signaling and cell surface expression\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    . In a rat model of reversible podocyte injury and proteinuria, phosphorylated nephrin temporally colocalized with endocytic structures coincident with upregulation of ShcA expression.\n                    <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                    biotinylation assays confirmed that nephrin expression decreased at the cell surface and correspondingly increased in the cytosol during the injury time course. Finally, immunostaining in kidney biopsy specimens demonstrated overexpression of ShcA in several human proteinuric kidney diseases compared with normal conditions. Our results suggest that increases in ShcA perturb nephrin phosphosignaling dynamics, leading to aberrant nephrin turnover and slit diaphragm disassembly.\n                  <\/jats:p>","DOI":"10.1681\/asn.2017030285","type":"journal-article","created":{"date-parts":[[2017,10,10]],"date-time":"2017-10-10T20:40:16Z","timestamp":1507668016000},"page":"92-103","source":"Crossref","is-referenced-by-count":27,"title":["ShcA Adaptor Protein Promotes Nephrin Endocytosis and Is Upregulated in Proteinuric Nephropathies"],"prefix":"10.1681","volume":"29","author":[{"given":"Claire E.","family":"Martin","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly A.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamine","family":"Aoudjit","sequence":"additional","affiliation":[{"name":"Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manali","family":"Tilak","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Eremina","sequence":"additional","affiliation":[{"name":"The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Rod","family":"Hardy","sequence":"additional","affiliation":[{"name":"The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Quaggin","sequence":"additional","affiliation":[{"name":"The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; and"},{"name":"Feinberg Cardiovascular Research Institute and Division of Nephrology and Hypertension, Northwestern University of Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Takano","sequence":"additional","affiliation":[{"name":"Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, 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