Direct comparison of manganese detoxification/efflux proteins and molecular characterization of ZnT10 protein as a manganese transporter

Yukina Nishito, Natsuko Tsuji, Hitomi Fujishiro, Taka Aki Takeda, Tomohiro Yamazaki, Fumie Teranishi, Fumiko Okazaki, Ayu Matsunaga, Karin Tuschl, Rajini Rao, Satoshi Kono, Hiroaki Miyajima, Hiroshi Narita, Seiichiro Himeno, Taiho Kambe

Research output: Contribution to journalArticle

Abstract

Manganese homeostasis involves coordinated regulation of specific proteins involved in manganese 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 manganese detoxification/ efflux, by evaluating their ability to reduce manganese toxicity in chicken DT40 cells, finding that human ZnT10 (hZnT10) was the most significant contributor.Adomain swapping and substitution analysis between hZnT10 and the zincspecific transporter hZnT1 showed that residue Asn43, which corresponds to the His residue constituting the potential intramembranous zinc coordination site in other ZnT transporters, is necessary to impart hZnT10's unique manganese mobilization activity; residues Cys52 and Leu242 in transmembrane domains II and V play a subtler role in controlling the metal specificity of hZnT10. Interestingly, the His3Asn reversion mutant in hZnT1 conferred manganese transport activity and loss of zinc transport activity. These results provide important information about manganese detoxification/efflux mechanisms in vertebrate cells as well as the molecular characterization of hZnT10 as a manganese transporter.

Original languageEnglish (US)
Pages (from-to)14773-14787
Number of pages15
JournalJournal of Biological Chemistry
Volume291
Issue number28
DOIs
StatePublished - Jul 8 2016

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Detoxification
Manganese
Proteins
Zinc
Metals
Toxicity
Vertebrates
Chickens
Homeostasis
Substitution reactions
Substrates

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Direct comparison of manganese detoxification/efflux proteins and molecular characterization of ZnT10 protein as a manganese transporter. / Nishito, Yukina; Tsuji, Natsuko; Fujishiro, Hitomi; Takeda, Taka Aki; Yamazaki, Tomohiro; Teranishi, Fumie; Okazaki, Fumiko; Matsunaga, Ayu; Tuschl, Karin; Rao, Rajini; Kono, Satoshi; Miyajima, Hiroaki; Narita, Hiroshi; Himeno, Seiichiro; Kambe, Taiho.

In: Journal of Biological Chemistry, Vol. 291, No. 28, 08.07.2016, p. 14773-14787.

Research output: Contribution to journalArticle

Nishito, Y, Tsuji, N, Fujishiro, H, Takeda, TA, Yamazaki, T, Teranishi, F, Okazaki, F, Matsunaga, A, Tuschl, K, Rao, R, Kono, S, Miyajima, H, Narita, H, Himeno, S & Kambe, T 2016, 'Direct comparison of manganese detoxification/efflux proteins and molecular characterization of ZnT10 protein as a manganese transporter', Journal of Biological Chemistry, vol. 291, no. 28, pp. 14773-14787. https://doi.org/10.1074/jbc.M116.728014
Nishito, Yukina ; Tsuji, Natsuko ; Fujishiro, Hitomi ; Takeda, Taka Aki ; Yamazaki, Tomohiro ; Teranishi, Fumie ; Okazaki, Fumiko ; Matsunaga, Ayu ; Tuschl, Karin ; Rao, Rajini ; Kono, Satoshi ; Miyajima, Hiroaki ; Narita, Hiroshi ; Himeno, Seiichiro ; Kambe, Taiho. / Direct comparison of manganese detoxification/efflux proteins and molecular characterization of ZnT10 protein as a manganese transporter. In: Journal of Biological Chemistry. 2016 ; Vol. 291, No. 28. pp. 14773-14787.
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