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Blood. 2007 Mar 1;109(5):2205-9. Epub 2006 Oct 31.

Evidence for the multimeric structure of ferroportin.

Author information

1
Department of Pathology, School of Medicine, University of Utah, Salt Lake City, UT 84132, USA.

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.

PMID:
17077321
PMCID:
PMC1801059
DOI:
10.1182/blood-2006-06-032516
[Indexed for MEDLINE]
Free PMC Article
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