title: Haemochromatosis protein is expressed on the terminal web of enterocytes in proximal small intestine of the rat.
abstract: The haemochromatosis protein (HFE) is an important regulator of body iron stores. In the liver, HFE is required for appropriate expression of hepcidin, a humoral mediator of iron absorption. HFE is also present in enterocytes, though its function in the intestine is unknown; it is not intrinsically required for iron absorption, but can augment iron absorption when over-expressed-independent of hepcidin regulation by the liver. In this study, an antibody was raised against rat HFE and validated by enzyme-linked immunosorbent assay, Western blot and quenching of antibody function by the immunising peptide. The sub-cellular location of HFE in enterocytes of iron-deficient and control rats was determined by double-labelling experiments with markers for the microvillus membrane, terminal web, early endosomes, lysosomes and the transferrin receptor. Parallel studies were performed for the primary iron absorption protein, divalent metal transporter 1 (DMT1). HFE co-localised exclusively with the terminal web of intestinal enterocytes. HFE expression was increased in iron deficiency, consistent with a second regulatory role for HFE in iron absorption, independent of hepcidin from the liver. DMT1 was localised primarily on the microvillus membrane, but did partially co-localise with HFE raising the possibility that the two proteins may interact to regulate iron absorption.
authors.affiliation: M311, Physiology, School of Biomedical and Chemical Sciences, The University of Western Australia, Crawley, WA 6009, Western Australia.
authors.forename: A R
authors.initials: AR
authors.lastname: West
authors.forename: C
authors.initials: C
authors.lastname: Thomas
authors.forename: J
authors.initials: J
authors.lastname: Sadlier
authors.forename: P S
authors.initials: PS
authors.lastname: Oates
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D020895:Enterocytes / Q000378:metabolism* / Q000648:ultrastructure; D015870:Gene Expression; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism; D000090463:Iron Deficiencies; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000378:metabolism; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D017931:DNA Primers; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D000099236:Solute Carrier Family 11, Member 2; C484232:HFE protein, rat