Abstract
Abstract Ferroportin (Fpn) (IREG1, SLC40A1, MTP1) is an iron transporter, and mutations in Fpn result in a genetically dominant form of iron overload disease. Previously, we demonstrated that Fpn is a multimer and that mutations in Fpn are dominant negative. Other studies have suggested that Fpn is not a multimer and that overexpression or epitope tags might affect the localization, topology, or multimerization of Fpn. We generated wild-type Fpn with 3 different epitopes, GFP, FLAG, and c-myc, and expressed these constructs in cultured cells. Co-expression of any 2 different epitope-tagged proteins in the same cell resulted in their quantitative coimmunoprecipitation. Treatment of Fpn-GFP/Fpn-FLAG–expressing cells with crosslinking reagents resulted in the crosslinking of Fpn-GFP and Fpn-FLAG. Western analysis of rat glioma C6 cells or mouse bone marrow macrophages exposed to crosslinking reagents showed that endogenous Fpn is a dimer. These results support the hypothesis that the dominant inheritance of Fpn–iron overload disease is due to the dominant-negative effects of mutant Fpn proteins.
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Dates
Type | When |
---|---|
Created | 18 years, 9 months ago (Nov. 2, 2006, 3:26 a.m.) |
Deposited | 5 years, 9 months ago (Nov. 17, 2019, 2:33 p.m.) |
Indexed | 4 months, 1 week ago (April 22, 2025, 4:09 a.m.) |
Issued | 18 years, 10 months ago (Oct. 31, 2006) |
Published | 18 years, 10 months ago (Oct. 31, 2006) |
Published Online | 18 years, 10 months ago (Oct. 31, 2006) |
Published Print | 18 years, 5 months ago (March 1, 2007) |
@article{De_Domenico_2006, title={Evidence for the multimeric structure of ferroportin}, volume={109}, ISSN={1528-0020}, url={http://dx.doi.org/10.1182/blood-2006-06-032516}, DOI={10.1182/blood-2006-06-032516}, number={5}, journal={Blood}, publisher={American Society of Hematology}, author={De Domenico, Ivana and Ward, Diane McVey and Musci, Giovanni and Kaplan, Jerry}, year={2006}, month=oct, pages={2205–2209} }