The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Discovery of the ergothioneine transporter
Open accessAbstract
Variants of the SLC22A4 gene are associated with susceptibility to rheumatoid arthritis and Crohn's disease. SLC22A4 codes for an integral membrane protein, OCTN1, that has been presumed to carry organic cations like tetraethylammonium across the plasma membrane. Here, we show that the key substrate of this transporter is in fact ergothioneine (ET). Human OCTN1 was expressed in 293 cells. A substrate lead, stachydrine (alias proline betaine), was identified by liquid chromatography MS difference shading, a new substrate search strategy. Analysis of transport efficiency of stachydrine-related solutes, affinity, and Na + dependence indicates that the physiological substrate is ET. Efficiency of transport of ET was as high as 195 μl per min per mg of protein. By contrast, the carnitine transporter OCTN2 from rat did not transport ET at all. Because ET is transported >100 times more efficiently than tetraethylammonium and carnitine, we propose the functional name ETT (ET transporter) instead of OCTN1. ET, all of which is absorbed from food, is an intracellular antioxidant with metal ion affinity. Its particular purpose is unresolved. Cells with expression of ETT accumulate ET to high levels and avidly retain it. By contrast, cells lacking ETT do not accumulate ET, because their plasma membrane is virtually impermeable for this compound. The real-time PCR expression profile of human ETT, with strong expression in CD71 + cells, is consistent with a pivotal function of ET in erythrocytes. Moreover, prominent expression of ETT in monocytes and SLC22A4 polymorphism associations suggest a protective role of ET in chronic inflammatory disorders.
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Cites
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Cloning and characterization of a novel human pH‐dependent organic cation transporter, OCTN1
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Molecular and Functional Characterization of Organic Cation/Carnitine Transporter Family in Mice
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Ergothioneine; antioxidant potential, physiological function and role in disease
Cheah, I. K., & Halliwell, B. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.09.017 · Cited by 514
Antioxidants of Edible Mushrooms
Kozarski, M., Klaus, A., Jakovljevic, D., Todorovic, N., Vunduk, J., Petrović, P., Niksic, M., Vrvic, M., & Van Griensven, L. (2015) · Molecules · doi:10.3390/molecules201019489 · Cited by 413
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Metadata
- Authors
- Gründemann, D., Harlfinger, S., Golz, S., Geerts, A., Lazar, A., Berkels, R., Jung, N., Rubbert, A., & Schömig, E.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2005-03-28
- Volume
- 102
- Issue
- 14
- Pages
- 5256-5261
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1993933306
- Cited by
- 608
- References
- 25
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- green
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- Gründemann, D., Harlfinger, S., Golz, S., Geerts, A., Lazar, A., Berkels, R., Jung, N., Rubbert, A., & Schömig, E. (2005). Discovery of the ergothioneine transporter. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0408624102
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