{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T18:36:51Z","timestamp":1768070211439,"version":"3.49.0"},"reference-count":38,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2012,7,23]],"date-time":"2012-07-23T00:00:00Z","timestamp":1343001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:p>The slit diaphragm (SD) is an intercellular junction between renal glomerular epithelial cells (podocytes) that is essential for permselectivity in glomerular ultrafiltration. The SD components, nephrin and Neph1, assemble a signaling complex in a tyrosine phosphorylation dependent manner, and regulate the unique actin cytoskeleton of podocytes. Mutations in the <jats:italic>NPHS1<\/jats:italic> gene that encodes nephrin cause congenital nephrotic syndrome (CNS), which is characterized by the loss of the SD and massive proteinuria. Recently, we have identified the expression of the transmembrane glycoprotein signal regulatory protein \u03b1 (SIRP\u03b1) at the SD. In the present study, we analyzed the expression of SIRP\u03b1 in developing kidneys, in kidneys from CNS patients and in proteinuric rat models. The possibility that SIRP\u03b1 interacts with known SD proteins was also investigated. SIRP\u03b1 was concentrated at the SD junction during the maturation of intercellular junctions. In the glomeruli of CNS patients carrying mutations in <jats:italic>NPHS1<\/jats:italic>, where SD formation is disrupted, the expression of SIRP\u03b1 as well as Neph1 and nephrin was significantly decreased, indicating that SIRP\u03b1 is closely associated with the nephrin complex. Indeed, SIRP\u03b1 formed hetero\u2010oligomers with nephrin in cultured cells and in glomeruli. Furthermore, the cytoplasmic domain of SIRP\u03b1 was highly phosphorylated in normal glomeruli, and its phosphorylation was dramatically decreased upon podocyte injury <jats:italic>in\u2003vivo<\/jats:italic>. Thus, SIRP\u03b1 interacts with nephrin at the SD, and its phosphorylation is dynamically regulated in proteinuric states. Our data provide new molecular insights into the phosphorylation events triggered by podocyte injury.<\/jats:p><jats:p><jats:bold>Structured digital abstract<\/jats:bold><\/jats:p><jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>\u2002<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/P97710\">Sirp\u2010alpha<\/jats:ext-link>\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0915\">physically interacts<\/jats:ext-link>\u2003with\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/Q9R044\">Nephrin<\/jats:ext-link>\u2003by\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0006\">anti bait coimmunoprecipitation<\/jats:ext-link>\u2003(<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/mint.bio.uniroma2.it\/mint\/search\/interaction.do?interactionAc=MINT-8384298\">View interaction<\/jats:ext-link>)<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>\u2002<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/P97710\">Sirp\u2010alpha<\/jats:ext-link>\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0915\">physically interacts<\/jats:ext-link>\u2003with\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/Q9R044\">Nephrin<\/jats:ext-link>\u2003by\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0007\">anti tag coimmunoprecipitation<\/jats:ext-link>\u2003(<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/mint.bio.uniroma2.it\/mint\/search\/interaction.do?interactionAc=MINT-8384216\">View interaction<\/jats:ext-link>)<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1111\/j.1742-4658.2012.08682.x","type":"journal-article","created":{"date-parts":[[2012,7,2]],"date-time":"2012-07-02T20:39:28Z","timestamp":1341261568000},"page":"3010-3021","source":"Crossref","is-referenced-by-count":24,"title":["SIRP<b>\u03b1<\/b> interacts with nephrin at the podocyte slit diaphragm"],"prefix":"10.1111","volume":"279","author":[{"given":"Yuko","family":"Kajiho","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Harita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidetake","family":"Kurihara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeru","family":"Horita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsuko","family":"Matsunaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruko","family":"Tsurumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoichiro","family":"Kanda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriko","family":"Sugawara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichiro","family":"Miura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Sekine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seisuke","family":"Hattori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motoshi","family":"Hattori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Igarashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,7,23]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.1.1"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00719.x"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80057-X"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00020.2002"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E10-12-0929"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1106556"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.05.026"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000196717.94518.f0"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12539"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000130167.30769.55"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301689200"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27414"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04662"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806851200"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00948-07"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707247200"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00024-5"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00571.2009"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)02703-5"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1859"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2008.12.001"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00758-X"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.12.6887"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(03)00091-4"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.111.3.1255"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00308.x"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2012.02.030"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/17.suppl_9.20"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008080871"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.23.2637"},{"key":"e_1_2_8_32_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.721402.x"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.4.2004"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.0751502.x"},{"key":"e_1_2_8_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/386181a0"},{"key":"e_1_2_8_36_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00070.x"},{"key":"e_1_2_8_37_2","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/376543"},{"key":"e_1_2_8_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.2.435"},{"key":"e_1_2_8_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311274200"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1742-4658.2012.08682.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1742-4658.2012.08682.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T19:02:17Z","timestamp":1696705337000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/j.1742-4658.2012.08682.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7,23]]},"references-count":38,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2012,9]]}},"alternative-id":["10.1111\/j.1742-4658.2012.08682.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1742-4658.2012.08682.x","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,7,23]]}}}