{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:43:36Z","timestamp":1791283416132,"version":"4.1.0"},"reference-count":51,"publisher":"American Society of Hematology","issue":"8","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,2,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cobalamin (Cbl, vitamin B12) deficiency in humans is a cause of hematologic and neurologic disorders. We show here that the cellular export of Cbl, in contrast to the carrier- and receptor-dependent cellular import of Cbl, occurs by transmembrane transport of \u201cfree\u201d Cbl. Screening of candidate transporters by cellular gene silencing showed a role in cellular Cbl efflux of the ATP-binding cassette (ABC)\u2013drug transporter, ABCC1, alias multidrug resistance protein 1 (MRP1), which is present in the basolateral membrane of intestinal epithelium and in other cells. The ability of MRP1 to mediate ATP-dependent Cbl transport was confirmed by vesicular transport experiments, and a physiologic role of MRP1 in mammalian Cbl homeostasis is indicated by the phenotype of knockout mice with targeted disruption of MRP1. These animals have a reduced concentration of Cbl in plasma and in the storage organs liver and kidney. In contrast, Cbl accumulates in the terminal part of the intestine of these mice, suggesting a functional malabsorption because of a lower epithelial basolateral Cbl efflux. The identification of this Cbl export mechanism now allows the delineation of a coherent pathway for Cbl trafficking from food to the body cells.<\/jats:p>","DOI":"10.1182\/blood-2009-07-232587","type":"journal-article","created":{"date-parts":[[2009,11,6]],"date-time":"2009-11-06T21:34:15Z","timestamp":1257543255000},"page":"1632-1639","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":123,"title":["Identification of multidrug resistance protein 1 (MRP1\/ABCC1) as a molecular gate for cellular export of cobalamin"],"prefix":"10.1182","volume":"115","author":[{"given":"Rasmus","family":"Beedholm-Ebsen","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, University of Aarhus, \u00c5rhus, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen","family":"van de Wetering","sequence":"additional","affiliation":[{"name":"Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tore","family":"Hardlei","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Aarhus University Hospital, \u00c5rhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebba","family":"Nex\u00f8","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Aarhus University Hospital, \u00c5rhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piet","family":"Borst","sequence":"additional","affiliation":[{"name":"Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren K.","family":"Moestrup","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, University of Aarhus, \u00c5rhus, Denmark;"},{"name":"Department of Clinical Biochemistry, Aarhus 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