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Role of ferroportin‐1 (FPN‐1) in iron (Fe) handling by the kidney proximal tubule (PT)
Author(s) -
Thevenod Frank,
Wolff Natascha A.,
Lee WingKee,
Liu Wei,
Smith Craig P.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.602.15
Subject(s) - ferroportin , dmt1 , chemistry , kidney , intracellular , hepcidin , homeostasis , cell culture , immunostaining , microbiology and biotechnology , biochemistry , transporter , medicine , biology , immunohistochemistry , endocrinology , anemia , immunology , genetics , gene
Previous studies indicate that the kidney PT is involved in body Fe homeostasis: 1) Fe is filtered and reabsorbed by the kidney PT; 2) The divalent metal transporter DMT1 is expressed in lysosomes of PT cells where its expression is responsive to systemic Fe levels. Here we show by immunostaining that the iron exporter ferroportin‐1 (FPN‐1) is expressed in rat kidney cortex and localized to PT cells. FPN‐1 is also expressed in a cell line derived from the S1‐segment of rat PT at the mRNA and protein level. Fe over‐load with ferric ammonium citrate (FAC) or depletion with desferrioxamine (DF) do not change overall FPN‐1 protein expression in cultured PT cells, as evidenced by immunoblotting. However, immunofluorescence staining shows increased cell surface expression of FPN‐1 in FAC treated cells. This was confirmed using cell surface biotinylation and immunoprecipitation of FPN‐1. The results indicate that FPN‐1 is expressed intracellularly and in plasma membranes of kidney PT cells. Fe overload may induce redistribution of intracellular FPN‐1 to the plasma membrane, possibly to increase Fe exit from PT cells. The expression of Fe transport proteins, such as DMT1 and FPN‐1, that are regulated by Fe suggest that the kidney PT is involved in Fe homeostasis. Supported by DFG & Wellcome Trust.