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However, the molecular mechanisms regarding UT\u2010A1 trafficking, endocytosis, and degradation are still unclear. In this study, we identified the small GTPase Rab14 as a binding partner to the C terminus of UT\u2010A1 in a yeast 2\u2010hybrid assay. Interestingly, UT\u2010A1 binding is preferential for the GDP\u2010bound inactive form of Rab14. Coinjection of Rab14 in\n                    <jats:italic>Xenopus<\/jats:italic>\n                    oocytes results in a decrease of UT\u2010A1 urea transport activity, suggesting that Rab14 acts as a negative regulator of UT\u2010A1. We subsequently found that Rab14 reduces the cell membrane expression of UT\u2010A1, as evidenced by cell surface biotinylation. This effect is blocked by chlor\u2010promazine, an inhibitor of the clathrin\u2010mediated endocytic pathway, but not by filipin, an inhibitor of the caveolin\u2010mediated endocytic pathway. In kidney, Rab14 is mainly expressed in IMCD epithelial cells with a pattern identical to UT\u2010A1 expression. Consistent with its role in participating in clathrin\u2010mediated endocytosis, Rab14 localizes in nonlipid raft microdomains and codistributes with Rab5, a marker of the clathrin\u2010mediated endocytic pathway. Taken together, our study suggests that Rab14, as a novel UT\u2010A1 partner, may have an important regulatory function for UT\u2010A1 urea transport activity in the kidney inner medulla.\u2014Su, H., Liu, B., Fr\u00f6hlich, O., Ma, H., Sands, J. M., Chen, G., Small GTPase Rab14 down\u2010regulates UT\u2010A1 urea transport activity through enhanced clathrin\u2010dependent endocytosis. FASEB J. 27, 4100\u20134107 (2013).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-229294","type":"journal-article","created":{"date-parts":[[2013,6,25]],"date-time":"2013-06-25T00:25:51Z","timestamp":1372119951000},"page":"4100-4107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Small GTPase Rab14 down\u2010regulates UT\u2010A1 urea transport activity through enhanced clathrin\u2010dependent endocytosis"],"prefix":"10.1096","volume":"27","author":[{"given":"Hua","family":"Su","sequence":"first","affiliation":[{"name":"Department of Physiology Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingchen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of 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