Evidence for the multimeric structure of ferroportin.
Open accessAbstract
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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Modest increase in ferritin levels may reflect contribution of hepcidin-sensitive endogenous wild type homodimers that correctly localize to plasma membrane.
“Given that Fpn functions as a dimer [37], this modest increase in ferritin levels may reflect the contribution of hepcidin-sensitive endogenous wild type homodimers that correctly localize to the plasma membrane.”
From Host Iron Withholding Demands Siderophore Utilization for Candida glabrata to Survive Macrophage Killing (2011) · cites this paper as [37]
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Cites
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Self-citation
- Authors
- De Domenico, I., Ward, D. M., Musci, G., & Kaplan, J.
- Affiliations
- Department of Pathology, School of Medicine, University of Utah, Salt Lake City;
- University of Utah (US)
- University of Molise (IT)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2006-10-31
- Volume
- 109
- Issue
- 5
- Pages
- 2205-2209
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC1801059
- OpenAlex
- W2029167543
- Cited by
- 72
- References
- 21
- Citations by year
- 2025: 1 · 2023: 1 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 3 · 2014: 5 · 2013: 8 · 2012: 5
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi del Molise (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK070947, R01DK070947)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- ferroportin, SLC40A1, iron transporters, protein oligomerization, protein dimerization, epitope tagging, cross-linking reagents, co-immunoprecipitation, glioma cells, bone marrow-derived macrophages
- MeSH terms
- Ferroportin, Animals, Epitopes, Cell Line, Humans, Protein Binding, Cation Transport Proteins, Mice, Rats
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