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Direct Comparison of Manganese Detoxification/Efflux Proteins and Molecular Characterization of ZnT10 as a Manganese Transporter

Nishito, Y; Tsuji, N; Fujishiro, H; Takeda, TA; Yamazaki, T; Teranishi, F; Okazaki, F; ... Kambe, T; + view all (2016) Direct Comparison of Manganese Detoxification/Efflux Proteins and Molecular Characterization of ZnT10 as a Manganese Transporter. The Journal of Biological Chemistry , 291 (28) pp. 14773-14787. 10.1074/jbc.M116.728014. Green open access

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Abstract

Manganese (Mn) homeostasis involves coordinated regulation of specific proteins involved in Mn influx and efflux. However, the proteins that are involved in detoxification/efflux have not been completely resolved, nor has the basis by which they select their metal substrate. Here, we compared six proteins, which were reported to be involved in Mn detoxification/efflux, by evaluating their ability to reduce Mn toxicity in chicken DT40 cells, finding that human ZnT10 (hZnT10) was the most significant contributor. A domain swapping and substitution analysis between hZnT10 and a zinc-specific transporter hZnT1 showed that residue N43, which corresponds to the His residue constituting the potential intramembranous zinc coordination site in other ZnT transporters, is necessary to impart hZnT10's unique Mn mobilization activity; residues C52 and L242 in transmembrane domains II and V play a subtler role in controlling the metal specificity of hZnT10. Interestingly, the H->N reversion mutant in hZnT1 conferred Mn transport activity and loss of zinc transport activity. These results provide important information about Mn detoxification/efflux mechanisms in vertebrate cells as well as the molecular characterization of hZnT10 as a Mn transporter.

Type: Article
Title: Direct Comparison of Manganese Detoxification/Efflux Proteins and Molecular Characterization of ZnT10 as a Manganese Transporter
Open access status: An open access version is available from UCL Discovery
DOI: 10.1074/jbc.M116.728014
Publisher version: http://dx.doi.org/10.1074/jbc.M116.728014
Language: English
Additional information: Copyright © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. All rights reserved. This research was originally published in The Journal of Biological Chemistry. Nishito, Y; Tsuji, N; Fujishiro, H; Takeda, TA; Yamazaki, T; Teranishi, F; Okazaki, F; (2016) Direct Comparison of Manganese Detoxification/Efflux Proteins and Molecular Characterization of ZnT10 as a Manganese Transporter. The Journal of Biological Chemistry , 291 (28) pp. 14773-14787 © the American Society for Biochemistry and Molecular Biology.
Keywords: ATP13A family protein, SPCA1, efflux, ferroportin, manganese, metal homeostasis, substrate specificity, transporter, zinc
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1502435
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