title: Localization of the iron transport proteins Mobilferrin and DMT-1 in the duodenum: the surprising role of mucin.
abstract: There are two pathways for inorganic iron uptake in the intestine, the ferric pathway, mediated by the key protein mobilferrin, and the ferrous pathway, mediated by DMT-1. Previous studies reported that the amount of DMT-1 increased in the intestinal mucosa in iron deficiency and the increase was seen in the apical portion of the villus of the duodenal mucosa. Mobilferrin did not quantitatively increase but became localized at the cell membrane. However, studies on fresh tissue have not previously been performed and the localization to the microvillae has not been demonstrated. In order to more definitively localize these proteins immunofluorescent and electron microscopic studies were undertaken. Samples were also subjected to biochemical analysis and Western analysis. In iron-deficient animals both DMT-1 and Mobilferrin were concentrated in the apical surface of the villae. Electron microscopy revealed that the majority of this increase in the amount of these proteins near the luminal surface was due to increased binding of the proteins to mucin in vesicles near the surface. A significant portion of the iron transport proteins was localized in the goblet cells and outside the cell in the luminal mucin, as demonstrated by immunofluorescence, electron microscopy, and isolation of the mucin by cesium chloride gradient centrifugation and Western analysis. A new model for the transport of metal ions was suggested. The metal transport proteins travel from vesicles inside the cell out to the lumen mucin. This increases the surface area and allows a greater portion of the lumen contents to be exposed to the binding proteins. Once the metal is bound to the externalized protein it is internalized into the cell. This explains many of the unique properties of the iron-binding proteins and suggests that it may be a more general model for the absorption of other nutrients.
authors.affiliation: University of South Alabama, Mobile, Alabama, USA.
authors.forename: Marcia
authors.initials: M
authors.lastname: Simovich
authors.forename: Lucille N
authors.initials: LN
authors.lastname: Hainsworth
authors.forename: P A
authors.initials: PA
authors.lastname: Fields
authors.forename: Jay N
authors.initials: JN
authors.lastname: Umbreit
authors.forename: Marcel E
authors.initials: ME
authors.lastname: Conrad
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D027682:Cation Transport Proteins / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism* / Q000648:ultrastructure; D005110:Extracellular Space / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006031:Glycosylation; D033862:Iron-Binding Proteins / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008871:Microvilli / Q000378:metabolism; D009077:Mucins / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D014018:Tissue Distribution; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D033862:Iron-Binding Proteins; D009077:Mucins; D000099236:Solute Carrier Family 11, Member 2; C085511:mobilferrin