{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T03:19:52Z","timestamp":1778901592914,"version":"3.51.4"},"reference-count":53,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["AHA24POST1191892"],"award-info":[{"award-number":["AHA24POST1191892"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL141131"],"award-info":[{"award-number":["HL141131"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"abstract":"<jats:p>\n                    KRIT1 plays a key role in regulating the barrier function of endothelial cells, where it localizes to the adherens junctions, cytoplasm, and nucleus. However, how subcellular localization may regulate KRIT1 remains unclear. Here, we investigate what effect nuclear localization has on its ability to stabilize the endothelial barrier. We generated a KRIT1 mutant lacking the endogenous nuclear localization signal (NLS) and a nuclear\u2010targeted KRIT1 isoform created by attaching the NLS of simian virus 40 and expressed these constructs in cells depleted of endogenous KRIT1. After confirming the relative non\u2010nuclear (KRIT1\n                    <jats:sup>\u0394NLS<\/jats:sup>\n                    ) and nuclear (KRIT1\n                    <jats:sup>NLS+<\/jats:sup>\n                    ) enrichment of these constructs using confocal microscopy and cellular fractionation, we assessed whether these constructs were able to functionally rescue phenotypes characteristic of KRIT1\u2010depleted cells. Our results showed that nuclear localized KRIT1 remains fully functional. However, the KRIT1\n                    <jats:sup>\u0394NLS<\/jats:sup>\n                    construct failed to rescue the KRIT1 depletion phenotype. KRIT1\n                    <jats:sup>\u0394NLS<\/jats:sup>\n                    also disrupted binding to ICAP1\u03b1, as shown by co\u2010immunoprecipitation. To determine whether the loss of function was due to loss of ICAP1\u03b1\u2010mediated conformational change or altered localization, we incorporated two mutants known to disrupt the N\u2010 to C\u2010terminal interaction in KRIT1,\n                    <jats:sup>192<\/jats:sup>\n                    NPXY\n                    <jats:sup>195<\/jats:sup>\n                    \u2192 APAA or W688A into our KRIT1\n                    <jats:sup>\u0394NLS<\/jats:sup>\n                    and KRIT1\n                    <jats:sup>NLS+<\/jats:sup>\n                    constructs. The presence of these additional mutations had unexpected effects on nuclear localization of KRIT1\n                    <jats:sup>\u0394NLS<\/jats:sup>\n                    and KRIT1\n                    <jats:sup>NLS+<\/jats:sup>\n                    but were able to restore barrier\u2010stabilizing function to KRIT1\n                    <jats:sup>\u0394NLS<\/jats:sup>\n                    . Overall, our findings provide key insights into the role of ICAP1\u03b1 binding and nuclear localization in the regulation of KRIT1 and raise new questions regarding potentially novel functions of KRIT1 in the nucleus.\n                  <\/jats:p>","DOI":"10.1111\/febs.70579","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T03:03:56Z","timestamp":1778468636000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>KRIT1<\/scp>\n                    nuclear localization does not impair\n                    <scp>KRIT1<\/scp>\n                    \u2010dependent regulation of endothelial barrier permeability and cell homeostasis"],"prefix":"10.1111","author":[{"given":"Andrea","family":"Perrelli","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology University of Rochester Medical Center  NY 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