{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:00:48Z","timestamp":1761217248829},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T00:00:00Z","timestamp":1234224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Motil. Cytoskeleton"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Podocytes are epithelial cells that line the outer aspect of renal blood vessels and provide a platform for the kidney's filtering apparatus, the slit diaphragm. Mutations in \u03b1\u2010actinin\u20104, an actin bundling protein highly expressed in podocytes, result in increased affinity for actin and cause a familial form of focal segmental glomerulosclerosis. We hypothesized that such gain\u2010of\u2010affinity mutations would override \u03b1\u2010actinin\u20104's sensitivity to regulatory factors such as calcium (acting via two EF\u2010hand motifs), and phosphoinositides. We generated calcium\u2010 (mutEF) and phosphoinositide\u2010 (mutPI) insensitive variants of \u03b1\u2010actinin\u20104, comparing their properties to a disease\u2010associated mutant (K256E) and to the wildtype (wt) protein. \u03b1\u2010Actinin\u20104<jats:sup>mutPI<\/jats:sup> displayed increased affinity for actin, while the affinity of \u03b1\u2010actinin\u20104<jats:sup>mutEF<\/jats:sup> was unchanged. Addition of calcium to actin sedimentation assays caused a decrease in the association of \u03b1\u2010actinin\u20104<jats:sup>wt<\/jats:sup> with filamentous actin, while phosphoinositides generally increased this association. Similar to \u03b1\u2010actinin\u20104<jats:sup>K256E<\/jats:sup>, \u03b1\u2010actinin\u20104<jats:sup>mutPI<\/jats:sup> was mislocalized in cultured podocytes, being preferentially associated with filamentous actin and focal adhesions. Fluorescence recovery after photobleaching experiments revealed a rapid turnover of \u03b1\u2010actinin\u20104<jats:sup>wt<\/jats:sup> and \u03b1\u2010actinin\u20104<jats:sup>mutEF<\/jats:sup> along stress fibers and focal adhesions, while the turnover of \u03b1\u2010actinin\u20104<jats:sup>K256E<\/jats:sup> and \u03b1\u2010actinin\u20104<jats:sup>mutPI<\/jats:sup> was dramatically reduced at these subcellular locales. Equibiaxial mechanical stimulation of podocytes, a mimic of intraglomerular forces, reduced podocyte surface area by 50%; this decrease was more severe (70%) in the presence of high\u2010affinity mutants of \u03b1\u2010actinin\u20104. These data suggest that dynamic regulation of \u03b1\u2010actinin\u20104\/actin interactions may be necessary for maintaining podocyte structure in response to glomerular hydrostatic forces. Cell Motil. Cytoskeleton, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/cm.20339","type":"journal-article","created":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T18:25:13Z","timestamp":1234290313000},"page":"166-178","source":"Crossref","is-referenced-by-count":20,"title":["Modulating \u03b1\u2010actinin\u20104 dynamics in podocytes"],"prefix":"10.1002","volume":"66","author":[{"given":"Jean\u2010Louis R.","family":"Michaud","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Hosseini\u2010Abardeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Farah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris R. J.","family":"Kennedy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,10]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M213288200"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500631200"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/359150a0"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.01-09-0465"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00220"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.140.6.1383"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.14.4917-4928.2003"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/73456"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02542"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.2.4.778-787.2003"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000059864.88610.5E"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5001665"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cm.20007"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00020.2002"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/35007077"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1592"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00711.x"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702451104"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106215"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020167"}],"container-title":["Cell Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcm.20339","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cm.20339","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T19:08:16Z","timestamp":1699902496000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cm.20339"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,2,10]]},"references-count":20,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2009,3]]}},"alternative-id":["10.1002\/cm.20339"],"URL":"https:\/\/doi.org\/10.1002\/cm.20339","archive":["Portico"],"relation":{},"ISSN":["0886-1544"],"issn-type":[{"value":"0886-1544","type":"print"}],"subject":[],"published":{"date-parts":[[2009,2,10]]}}}