Iron-dependent regulation of transferrin receptor expression in Trypanosoma brucei
Open accessAbstract
Transferrin is an essential growth factor for African trypanosomes. Here we show that expression of the trypanosomal transferrin receptor, which bears no structural similarity with mammalian transferrin receptors, is regulated by iron availability. Iron depletion of bloodstream forms of Trypanosoma brucei with the iron chelator deferoxamine resulted in a 3-fold up-regulation of the transferrin receptor and a 3-fold increase of the transferrin uptake rate. The abundance of expression site associated gene product 6 (ESAG6) mRNA, which encodes one of the two subunits of the trypanosome transferrin receptor, is regulated 5-fold by a post-transcriptional mechanism. In mammalian cells the stability of transferrin receptor mRNA is controlled by iron regulatory proteins (IRPs) binding to iron-responsive elements (IREs) in the 3′-untranslated region (UTR). Therefore, the role of a T. brucei cytoplasmic aconitase (TbACO) that is highly related to mammalian IRP-1 was investigated. Iron regulation of the transferrin receptor was found to be unaffected in δaco::NEO/δaco::HYG null mutants generated by targeted disruption of the TbACO gene. Thus, the mechanism of post-transcriptional transferrin receptor regulation in trypanosomes appears to be distinct from the IRE/IRP paradigm. The transferrin uptake rate was also increased when trypanosomes were transferred from medium supplemented with foetal bovine serum to medium supplemented with sera from other vertebrates. Due to varying binding affinities of the trypanosomal transferrin receptor for transferrins of different species, serum change can result in iron starvation. Thus, regulation of transferrin receptor expression may be a fast compensatory mechanism upon transmission of the parasite to a new host species.
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The bloodstream form of T. brucei acquires Fe from Tf by receptor-mediated endocytosis of host transferrin, a process regulated by Fe availability.
“The bloodstream form of Trypanosoma brucei acquires Fe from Tf by receptor-mediated endocytosis by a process that is regulated by Fe availability.”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [93]
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References 49 · Cited by 43
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- Chaudhri, M., Steverding, D., Kittelberger, D., Tjia, S. and Overath, P. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 6443-6447
- Hentze, M. W. and Ku$ hn, L. C. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 8175-8182
- Haile, D. J., Rouault, T. A., Harford, J. B., Kennedy, M. C., Blondin, G. A., Beinert, H. and Klausner, R. D. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 11735-11739
- Iwai, K., Drake, S. K., Wehr, N. B., Weissman, A. M., LaVaute, T., Minato, N., Klausner, R. D., Levine, R. L. and Rouault, T. A. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 4924-4928
- Koeller, D. M., Casey, J. L., Hentze, M. W., Gerhardt, E. M., Chan, L. N. L., Klausner, R. D. and Harford, J. B. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 3574-3578
- Schalinske, K. L., Blemings, K. P., Steffen, D. W., Chen, O. S. and Eisenstein, R. S. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 10681-10686
- Authors
- FAST, B., KREMP, K., BOSHART, M., & STEVERDING, D.
- Affiliations
- Max Planck Institute of Biochemistry (DE)
- Heidelberg University (DE)
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 1999-09-05
- Volume
- 342
- Issue
- 3
- Pages
- 691-696
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1220511
- OpenAlex
- W2058145203
- Cited by
- 43
- References
- 49
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2021: 2 · 2019: 1 · 2018: 2 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 2
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
- Keywords
- transferrin receptor, Trypanosoma brucei, iron regulation, transferrin uptake, post-transcriptional regulation, iron regulatory proteins, iron-responsive element, aconitase, deferoxamine, iron starvation, bloodstream forms
- MeSH terms
- Aconitate Hydratase, Animals, Cattle, Cell Line, Cytoplasm, Gene Expression Regulation, Iron, Iron-Sulfur Proteins, Protein Processing, Post-Translational, Receptors, Transferrin, RNA, Messenger, Transferrin, Trypanosoma brucei brucei, Blotting, Northern, RNA-Binding Proteins, Iron-Regulatory Proteins, Iron Regulatory Protein 1, Rats
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