Linked Life Data

10085150

Source:http://linkedlifedata.com/resource/pubmed/id/10085150

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
1999-4-29
pubmed:abstractText
HFE is the protein product of the gene mutated in the autosomal recessive disease hereditary hemochromatosis (Feder, J. N., Gnirke, A., Thomas, W., Tsuchihashi, Z., Ruddy, D. A., Basava, A., Dormishian, F., Domingo, R. J., Ellis, M. C., Fullan, A., Hinton, L. M., Jones, N. L., Kimmel, B. E., Kronmal, G. S., Lauer, P., Lee, V. K., Loeb, D. B., Mapa, F. A., McClelland, E., Meyer, N. C., Mintier, G. A., Moeller, N., Moore, T., Morikang, E., Prasss, C. E., Quintana, L., Starnes, S. M., Schatzman, R. C., Brunke, K. J., Drayna, D. T., Risch, N. J., Bacon, B. R., and Wolff, R. R. (1996) Nat. Genet. 13, 399-408). At the cell surface, HFE complexes with transferrin receptor (TfR), increasing the dissociation constant of transferrin (Tf) for its receptor 10-fold (Gross, C. N., Irrinki, A., Feder, J. N., and Enns, C. A. (1998) J. Biol. Chem. 273, 22068-22074; Feder, J. N., Penny, D. M., Irrinki, A., Lee, V. K., Lebron, J. A., Watson, N. , Tsuchihashi, Z., Sigal, E., Bjorkman, P. J., and Schatzman, R. C. (1998) Proc. Natl. Acad. Sci. U S A 95, 1472-1477). HFE does not remain at the cell surface, but traffics with TfR to Tf-positive internal compartments (Gross et al., 1998). Using a HeLa cell line in which the expression of HFE is controlled by tetracycline, we show that the expression of HFE reduces 55Fe uptake from Tf by 33% but does not affect the endocytic or exocytic rates of TfR cycling. Therefore, HFE appears to reduce cellular acquisition of iron from Tf within endocytic compartments. HFE specifically reduces iron uptake from Tf, as non-Tf-mediated iron uptake from Fe-nitrilotriacetic acid is not altered. These results explain the decreased ferritin levels seen in our HeLa cell system and demonstrate the specific control of HFE over the Tf-mediated pathway of iron uptake. These results also have implications for the understanding of cellular iron homeostasis in organs such as the liver, pancreas, heart, and spleen that are iron loaded in hereditary hemochromatotic individuals lacking functional HFE.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9022-8
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:10085150-Biological Transport, pubmed-meshheading:10085150-Endocytosis, pubmed-meshheading:10085150-Exocytosis, pubmed-meshheading:10085150-Gene Expression Regulation, pubmed-meshheading:10085150-HLA Antigens, pubmed-meshheading:10085150-HeLa Cells, pubmed-meshheading:10085150-Hemochromatosis, pubmed-meshheading:10085150-Histocompatibility Antigens Class I, pubmed-meshheading:10085150-Humans, pubmed-meshheading:10085150-Iodine Radioisotopes, pubmed-meshheading:10085150-Iron, pubmed-meshheading:10085150-Iron Radioisotopes, pubmed-meshheading:10085150-Kinetics, pubmed-meshheading:10085150-Membrane Proteins, pubmed-meshheading:10085150-Nitrilotriacetic Acid, pubmed-meshheading:10085150-Receptors, Transferrin, pubmed-meshheading:10085150-Tetracyclines, pubmed-meshheading:10085150-Transferrin
pubmed:year
1999
pubmed:articleTitle
The hereditary hemochromatosis protein, HFE, specifically regulates transferrin-mediated iron uptake in HeLa cells.
pubmed:affiliation
Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland, Oregon 97201-3098, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.