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Axial resolution is maximized by concurrently applied total internal reflection fluorescence and epifluorescence-structured light. We found that transferrin receptors are delivered selectively from clathrin-coated pits on the plasma membrane into a specific subpopulation of endosomes enriched in the multivalent Rab GTPase and phosphoinositide-binding protein Rabenosyn-5. Depletion of Rabenosyn-5, but not of other early endosomal proteins such as early endosome antigen 1, resulted in impaired transferrin uptake and lysosomal degradation of transferrin receptors. These studies reveal a critical role for Rabenosyn-5 in determining the fate of transferrin receptors internalized by clathrin-mediated endocytosis and, more broadly, a mechanism whereby the delivery of cargo from the plasma membrane into specific early endosome subpopulations is required for its appropriate intracellular traffic.<\/jats:p>","DOI":"10.1073\/pnas.1115495109","type":"journal-article","created":{"date-parts":[[2012,1,31]],"date-time":"2012-01-31T01:24:54Z","timestamp":1327973094000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":84,"title":["Rabenosyn-5 defines the fate of the transferrin receptor following clathrin-mediated endocytosis"],"prefix":"10.1073","volume":"109","author":[{"given":"Deanna M.","family":"Navaroli","sequence":"first","affiliation":[{"name":"Program in Molecular Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl D.","family":"Bellv\u00e9","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Group, University of Massachusetts Medical School, Worcester MA 01605; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive","family":"Standley","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Group, University of Massachusetts Medical School, Worcester MA 01605; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence M.","family":"Lifshitz","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Group, University of Massachusetts Medical School, Worcester MA 01605; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Cardia","sequence":"additional","affiliation":[{"name":"RXi Pharmaceuticals Corporation, Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lambright","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Leonard","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin E.","family":"Fogarty","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Group, University of Massachusetts Medical School, Worcester MA 01605; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Corvera","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,1,30]]},"reference":[{"key":"e_1_1_2_17_10_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.12.1.575"},{"key":"e_1_1_2_17_10_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508832103"},{"key":"e_1_1_2_17_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.12.038"},{"key":"e_1_1_2_17_10_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.032"},{"key":"e_1_1_2_17_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2009.11.007"},{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1101\/SQB.1995.060.01.080"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0955-0674(95)80013-1"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1315"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.78.081307.110540"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.08.010"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.024"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0909-1049"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1930"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1929"},{"key":"e_1_3_3_10_2","first-page":"99","article-title":"The early endosome: A busy sorting station for proteins at the crossroads","volume":"25","author":"Jovic M","year":"2010","unstructured":"M Jovic, M Sharma, J Rahajeng, S Caplan, The early endosome: A busy sorting station for proteins at the crossroads. 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