{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:06:38Z","timestamp":1791173198252,"version":"4.1.0"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,1,2]]},"abstract":"<jats:p>Agonist-dependent desensitization and internalization of G\n protein-coupled receptors (GPCR) are mediated by the binding of\n arrestins to phosphorylated receptors. The affinity of arrestins for\n the phosphorylated GPCR regulates the ability of the internalized\n receptor to be dephosphorylated and recycled back to the plasma\n membrane. In this study, we show that the naturally occurring loss\n of function vasopressin receptor mutation R137H, which is associated\n with familial nephrogenic diabetes insipidus, induces constitutive\n arrestin-mediated desensitization. In contrast to the wild-type\n vasopressin receptor, the nonsignaling R137H receptor is phosphorylated\n and sequestered in arrestin-associated intracellular vesicles even in\n the absence of agonist. Eliminating molecular determinants on the\n receptor that promote high affinity arrestin\u2013receptor interaction\n reestablishes plasma membrane localization and the ability of the\n mutated receptors to signal. These findings suggest that unregulated\n desensitization can contribute to the etiology of a GPCR-based disease,\n implying that pharmacological targeting of GPCR desensitization may be\n therapeutically beneficial.<\/jats:p>","DOI":"10.1073\/pnas.98.1.93","type":"journal-article","created":{"date-parts":[[2012,7,30]],"date-time":"2012-07-30T13:19:48Z","timestamp":1343654388000},"page":"93-98","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":225,"title":["Constitutive arrestin-mediated desensitization of a human vasopressin receptor mutant associated with nephrogenic diabetes insipidus"],"prefix":"10.1073","volume":"98","author":[{"given":"Larry S.","family":"Barak","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute Laboratories and Departments of\r Cell Biology and Medicine, Duke University Medical Center, Durham, NC\r 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Oakley","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute Laboratories and Departments of\r Cell Biology and Medicine, Duke University Medical Center, Durham, NC\r 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane A.","family":"Laporte","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute Laboratories and Departments of\r Cell Biology and Medicine, Duke University Medical Center, Durham, NC\r 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc G.","family":"Caron","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute Laboratories and Departments of\r Cell Biology and Medicine, Duke University Medical Center, Durham, NC\r 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