{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T16:50:30Z","timestamp":1792255830758,"version":"4.4.0"},"reference-count":43,"publisher":"American Society for Cell Biology (ASCB)","issue":"14","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2011,7,15]]},"abstract":"<jats:p>Activation of Rap1 small GTPases stabilizes cell\u2013cell junctions, and this activity requires Krev Interaction Trapped gene 1 (KRIT1). Loss of KRIT1 disrupts cardiovascular development and causes autosomal dominant familial cerebral cavernous malformations. Here we report that native KRIT1 protein binds the effector loop of Rap1A but not H-Ras in a GTP-dependent manner, establishing that it is an authentic Rap1-specific effector. By modeling the KRIT1\u2013Rap1 interface we designed a well-folded KRIT1 mutant that exhibited a \u223c40-fold-reduced affinity for Rap1A and maintained other KRIT1-binding functions. Direct binding of KRIT1 to Rap1 stabilized endothelial cell\u2013cell junctions in vitro and was required for cardiovascular development in vivo. Mechanistically, Rap1 binding released KRIT1 from microtubules, enabling it to locate to cell\u2013cell junctions, where it suppressed Rho kinase signaling and stabilized the junctions. These studies establish that the direct physical interaction of Rap1 with KRIT1 enables the translocation of microtubule-sequestered KRIT1 to junctions, thereby supporting junctional integrity and cardiovascular development.<\/jats:p>","DOI":"10.1091\/mbc.e11-02-0157","type":"journal-article","created":{"date-parts":[[2011,6,3]],"date-time":"2011-06-03T07:38:28Z","timestamp":1307086708000},"page":"2509-2519","source":"Crossref","is-referenced-by-count":66,"title":["A mechanism of Rap1-induced stabilization of endothelial cell\u2013cell junctions"],"prefix":"10.1091","volume":"22","author":[{"given":"Jian J.","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A.","family":"Stockton","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, CA 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