{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:29:20Z","timestamp":1791419360906,"version":"4.3.3"},"reference-count":98,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,5,9]],"date-time":"2018-05-09T00:00:00Z","timestamp":1525824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cobalamin [Cbl (or B\n                    <jats:sub>12<\/jats:sub>\n                    )] deficiency causes megaloblastic anemia and a variety of neuropathies. However, homeostatic mechanisms of cyanocobalamin (CNCbl) and other Cbls by vascular endothelial cells are poorly understood. Herein, we describe our investigation into whether cultured bovine aortic endothelial cells (BAECs) perform transcytosis of B12, namely, the complex formed between serum transcobalamin and B12, designated as holo\u2010 transcobalamin (holo\u2010TC). We show that cultured BAECs endocytose [\n                    <jats:sup>57<\/jats:sup>\n                    Co]\u2010CNCbl\u2010TC (source material)\n                    <jats:italic>via<\/jats:italic>\n                    the CD320 receptor. The bound Cbl is transported across the cell both\n                    <jats:italic>via<\/jats:italic>\n                    exocytosis in its free form, [\n                    <jats:sup>57<\/jats:sup>\n                    Co]\u2010CNCbl, and\n                    <jats:italic>via<\/jats:italic>\n                    transcytosis as [\n                    <jats:sup>57<\/jats:sup>\n                    Co]\u2010CNCbl\u2010TC. Transcellular mobilization of Cbl occurred in a bidirectional manner. A portion of the endocytosed [\n                    <jats:sup>57<\/jats:sup>\n                    Co]\u2010CNCbl was enzymatically processed by methylmalonic aciduria combined with homocystinuria type C (cblC) with subsequent formation of hydroxocobalamin, methylcobalamin, and adenosylcobalamin, which were also transported across the cell in a bidirectional manner. This demonstrates that transport mechanisms for Cbl in vascular endothelial cells do not discriminate between various \u03b2\u2010axial ligands of the vitamin. Competition studies with apoprotein\u2010 and holo\u2010TC and holo\u2010intrinsic factor showed that only holo\u2010TC was effective at inhibiting transcellular transport of Cbl. Incubation of BAECs with a blocking antibody against the extracellular domain of the CD320 receptor inhibited uptake and transcytosis by ~40%. This study reveals that endothelial cells recycle uncommitted intracellular Cbl for downstream usage by other cell types and suggests that the endothelium is self\u2010sufficient for the specific acquisition and subsequent distribution of circulating B\n                    <jats:sub>12<\/jats:sub>\n                    <jats:italic>via<\/jats:italic>\n                    the CD320 receptor. We posit that the endothelial lining of the vasculature is an essential component for the maintenance of serum\u2010 tissue homeostasis of B\n                    <jats:sub>12<\/jats:sub>\n                    .\u2014Hannibal, L., Bolisetty, K., Axhemi, A., DiBello, P. M., Quadros, E. V., Fedosov, S., Jacobsen, D. W. Transcellular transport of cobalamin in aortic endothelial cells.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    32, 5506\u20135519 (2018).\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.201701141rr","type":"journal-article","created":{"date-parts":[[2018,5,9]],"date-time":"2018-05-09T15:50:38Z","timestamp":1525881038000},"page":"5506-5519","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Transcellular transport of cobalamin in aortic endothelial cells"],"prefix":"10.1096","volume":"32","author":[{"given":"Luciana","family":"Hannibal","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Biochemistry and Metabolism, Department for Pediatrics Medical Center, University of Freiburg Freiburg Germany"},{"name":"Department of Cellular and Molecular Medicine Lerner Research Institute, Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keerthana","family":"Bolisetty","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine Lerner Research Institute, Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armend","family":"Axhemi","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine Lerner Research Institute, Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia M.","family":"DiBello","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine Lerner Research Institute, Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward V.","family":"Quadros","sequence":"additional","affiliation":[{"name":"Department of Medicine State University of New York (SUNY) Downstate Medical Center Brooklyn New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Fedosov","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald W.","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine Lerner Research Institute, Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-10-569186"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2016.00027"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msr124"},{"key":"e_1_2_7_5_1","volume-title":"Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline","author":"U.S. Institute of Medicine Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline","year":"1998"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb6001174"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-2199-9_18"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2012.76"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-232587"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-08-2852"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1999.277.1.G161"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2007.343"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.111.013458"},{"key":"e_1_2_7_14_1","first-page":"515","article-title":"Soluble transcobalamin receptor, sCD320, is present in human serum and relates to serum cobalamin \u2014 establishment and validation of an ELISA","volume":"50","author":"Arendt J. 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