{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:23:59Z","timestamp":1790263439555,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,10,27]],"date-time":"2014-10-27T00:00:00Z","timestamp":1414368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 DK-072084 and P01-GM067166."],"award-info":[{"award-number":["P01 DK-072084 and P01-GM067166."]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Traffic"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:p>Physiologic Cu levels regulate the intracellular location of the Cu <jats:styled-content style=\"fixed-case\">ATPase ATP7B<\/jats:styled-content>. Here, we determined the routes of Cu\u2010directed trafficking of endogenous <jats:styled-content style=\"fixed-case\">ATP7B<\/jats:styled-content> in the polarized hepatic cell line <jats:styled-content style=\"fixed-case\">WIF<\/jats:styled-content>\u2010B and in the liver <jats:italic>in vivo<\/jats:italic>. Copper (10\u2009\u00b5<jats:sc>m<\/jats:sc>) caused <jats:styled-content style=\"fixed-case\">ATP7B<\/jats:styled-content> to exit the trans\u2010Golgi network (<jats:styled-content style=\"fixed-case\">TGN<\/jats:styled-content>) in vesicles, which trafficked via large basolateral endosomes to the apical domain within 1\u2009h. Although perturbants of luminal acidification had little effect on the <jats:styled-content style=\"fixed-case\">TGN<\/jats:styled-content> localization of <jats:styled-content style=\"fixed-case\">ATP7B<\/jats:styled-content> in low Cu, they blocked delivery to the apical membrane in elevated Cu. If the vesicular proton\u2010pump inhibitor bafilomycin\u2010A1 <jats:styled-content style=\"fixed-case\">(Baf)<\/jats:styled-content> was present with Cu, <jats:styled-content style=\"fixed-case\">ATP7B<\/jats:styled-content> still exited the <jats:styled-content style=\"fixed-case\">TGN<\/jats:styled-content>, but accumulated in large endosomes located near the coverslip, in the basolateral region. <jats:styled-content style=\"fixed-case\">Baf<\/jats:styled-content> washout restored <jats:styled-content style=\"fixed-case\">ATP7B<\/jats:styled-content> trafficking to the apical domain. If <jats:styled-content style=\"fixed-case\">ATP7B<\/jats:styled-content> was staged apically in high Cu, <jats:styled-content style=\"fixed-case\">Baf<\/jats:styled-content> addition promoted the accumulation of <jats:styled-content style=\"fixed-case\">ATP7B<\/jats:styled-content> in subapical endosomes, indicating a blockade of apical recycling, with concomitant loss of <jats:styled-content style=\"fixed-case\">ATP7B<\/jats:styled-content> at the apical membrane. The retrograde pathway to the <jats:styled-content style=\"fixed-case\">TGN<\/jats:styled-content>, induced by Cu removal, was far less affected by <jats:styled-content style=\"fixed-case\">Baf<\/jats:styled-content> than the anterograde (Cu\u2010stimulated) case. Overall, loss of acidification\u2010impaired Cu\u2010regulated trafficking of <jats:styled-content style=\"fixed-case\">ATP7B<\/jats:styled-content> at two main sites: (i) sorting and exit from large basolateral endosomes and (ii) recycling via endosomes near the apical membrane.<\/jats:p><jats:p><jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tra12229-gra-0001.png\" xlink:title=\"image\"\/><\/jats:p>","DOI":"10.1111\/tra.12229","type":"journal-article","created":{"date-parts":[[2014,9,22]],"date-time":"2014-09-22T10:37:28Z","timestamp":1411382248000},"page":"1344-1365","source":"Crossref","is-referenced-by-count":39,"title":["Copper Directs <scp>ATP7B<\/scp> to the Apical Domain of Hepatic Cells via Basolateral Endosomes"],"prefix":"10.1111","volume":"15","author":[{"given":"Lydia K.","family":"Nyasae","sequence":"first","affiliation":[{"name":"Department of Cell Biology The Johns Hopkins School of Medicine  725 N. Wolfe Street Baltimore MD 20184 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Schell","sequence":"additional","affiliation":[{"name":"Department of Cell Biology The Johns Hopkins School of Medicine  725 N. Wolfe Street Baltimore MD 20184 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann L.","family":"Hubbard","sequence":"additional","affiliation":[{"name":"Department of Cell Biology The Johns Hopkins School of Medicine  725 N. 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