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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
16
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pubmed:dateCreated |
1996-9-12
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pubmed:abstractText |
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.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-1115794,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-113164,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-1245601,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-1336400,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-1382088,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-13828999,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-13852753,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-14481609,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-1455157,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-1695632,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-1848331,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-2463827,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-2553457,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-3286063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-3715376,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-3884427,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-3908480,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-3953773,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-4207620,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-5096637,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-5954821,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-6147223,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-618908,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-632241,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-6752952,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7357037,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7510321,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7512726,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7518253,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7533537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7538675,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7544804,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7575428,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7579068,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7615159,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7664754,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7713919,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7720568,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7768901,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7774585,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7803716,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7913804,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7937880,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-7979249,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8710919-8344937
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
93
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8612-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:8710919-Animals,
pubmed-meshheading:8710919-Homeostasis,
pubmed-meshheading:8710919-Rats,
pubmed-meshheading:8710919-Rabbits,
pubmed-meshheading:8710919-Male,
pubmed-meshheading:8710919-Kinetics,
pubmed-meshheading:8710919-Vitamin B 12,
pubmed-meshheading:8710919-Cell Membrane,
pubmed-meshheading:8710919-Cells, Cultured,
pubmed-meshheading:8710919-Rats, Wistar,
pubmed-meshheading:8710919-Protein Binding,
pubmed-meshheading:8710919-Transcobalamins,
pubmed-meshheading:8710919-Kidney Tubules, Proximal,
pubmed-meshheading:8710919-Endodermal Sinus Tumor,
pubmed-meshheading:8710919-Kidney Cortex,
pubmed-meshheading:8710919-Endocytosis,
pubmed-meshheading:8710919-Membrane Glycoproteins,
pubmed-meshheading:8710919-Receptors, LDL
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