{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:48:48Z","timestamp":1790970528814,"version":"4.1.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"16","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,8,6]]},"abstract":"<jats:p>Kidney cortex is a main target for circulating vitamin B12 (cobalamin) in complex with transcobalamin (TC). Ligand blotting of rabbit kidney cortex with rabbit 125I-TC-B12 and human TC-57Co-B12 revealed an exclusive binding to megalin, a 600-kDa endocytic receptor present in renal proximal tubule epithelium and other absorptive epithelia. The binding was Ca2+ dependent and inhibited by receptor-associated protein (RAP). Surface plasmon resonance analysis demonstrated a high-affinity interaction between purified rabbit megalin and rabbit TC-B12 but no measurable affinity of the vitamin complex for the homologous alpha 2-macroglobulin receptor (alpha 2MR)\/low density lipoprotein receptor related protein (LRP). 125I-TC-B12 was efficiently endocytosed in a RAP-inhibitable manner in megalin-expressing rat yolk sac carcinoma cells and in vivo microperfused rat proximal tubules. The radioactivity in the tubules localized to the endocytic compartments and a similar apical distribution in the proximal tubules was demonstrated after intravenous injection of 125I-TC-B12. The TC-B12 binding sites in the proximal tubule epithelium colocalized with megalin as shown by ligand binding to cryosections of rat kidney cortex, and the binding was inhibited by anti-megalin polyclonal antibody, EDTA, and RAP. These data show a novel nutritional dimension of megalin as a receptor involved in the cellular uptake of vitamin B12. The expression of megalin in absorptive epithelia in the kidney and other tissues including yolk sac and placenta suggests a role of the receptor in vitamin B12 homeostasis and fetal vitamin B12 supply.<\/jats:p>","DOI":"10.1073\/pnas.93.16.8612","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:32:33Z","timestamp":1027679553000},"page":"8612-8617","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":180,"title":["Megalin-mediated endocytosis of transcobalamin-vitamin-B12 complexes suggests a role of the receptor in vitamin-B12 homeostasis."],"prefix":"10.1073","volume":"93","author":[{"given":"S K","family":"Moestrup","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Kommunehospitalet University of Aarhus, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Birn","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Kommunehospitalet University of Aarhus, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P B","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Kommunehospitalet University of Aarhus, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C M","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Kommunehospitalet University of Aarhus, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P J","family":"Verroust","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Kommunehospitalet University of Aarhus, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R B","family":"Sim","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Kommunehospitalet University of Aarhus, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E I","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Kommunehospitalet University of Aarhus, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Nex\u00f8","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Kommunehospitalet University of Aarhus, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1996,8,6]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.93.16.8612","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:41:44Z","timestamp":1649860904000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.93.16.8612"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,8,6]]},"references-count":0,"journal-issue":{"issue":"16","published-print":{"date-parts":[[1996,8,6]]}},"alternative-id":["10.1073\/pnas.93.16.8612"],"URL":"https:\/\/doi.org\/10.1073\/pnas.93.16.8612","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,8,6]]},"assertion":[{"value":"1996-08-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}