Characterization of the human MATE2 proton-coupled polyspecific organic cation exporter

Toshinori Komatsu, Miki Hiasa, Takaaki Miyaji, Takuji Kanamoto, Takuya Matsumoto, Masato Otsuka, Yoshinori Moriyama, Hiroshi Omote

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Human multidrug and toxic compound extrusion 2 (hMATE2) is a kidney-specific isoform of hMATE1, an exporter of toxic organic cations (OCs) of exogenous and endogenous origins at the final excretion step in the kidneys and liver (Otsuka et al., 2005), and contains a splicing variant, MATE2K, that has an exon of hMATE2 deleted (Masuda et al., 2006). In the present study, we characterized the degree of expression and the transport properties of hMATE2. Quantitative PCR analysis with probes specific for hMATE2 indicated the presence of hMATE2 mRNA in the kidneys, which corresponded to 39% of total mRNA encoding both hMATE2 and hMATE2K. hMATE2-specific antibodies immunostained the renal urinary tubules. Upon expression in HEK293 cells, hMATE2 was localized in intracellular vesicular structures, and thus transport activity of tetraethylammonium (TEA), a typical substrate for MATE transporters, by the cells was not detected. The hMATE2 protein was purified and reconstituted into liposomes. An artificially imposed pH gradient (ΔpH) across the proteoliposomal membrane drove the uptake of TEA. Dissipation of ΔpH by ammonium sulfate effectively inhibited the TEA uptake, while that of the membrane potential by valinomycin had little effect. The profiles of cis-inhibition of TEA transport by hMATE2 and hMATE2K are similar to each other. Thus, both hMATE2 and hMATE2K equally operate in the human kidneys to extrude OCs into the urine.

Original languageEnglish
Pages (from-to)913-918
Number of pages6
JournalInternational Journal of Biochemistry and Cell Biology
Volume43
Issue number6
DOIs
Publication statusPublished - Jun 2011

Fingerprint

Poisons
Cations
Protons
Extrusion
Tetraethylammonium
Kidney
Membranes
Valinomycin
Messenger RNA
Proton-Motive Force
HEK293 Cells
Ammonium Sulfate
Liposomes
Liver
Membrane Potentials
Transport properties
Exons
Protein Isoforms
Urine
Polymerase Chain Reaction

Keywords

  • Brush border membrane
  • MATE
  • Organic cation transporter
  • Splicing variant
  • Urinary duct

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Characterization of the human MATE2 proton-coupled polyspecific organic cation exporter. / Komatsu, Toshinori; Hiasa, Miki; Miyaji, Takaaki; Kanamoto, Takuji; Matsumoto, Takuya; Otsuka, Masato; Moriyama, Yoshinori; Omote, Hiroshi.

In: International Journal of Biochemistry and Cell Biology, Vol. 43, No. 6, 06.2011, p. 913-918.

Research output: Contribution to journalArticle

Komatsu, Toshinori ; Hiasa, Miki ; Miyaji, Takaaki ; Kanamoto, Takuji ; Matsumoto, Takuya ; Otsuka, Masato ; Moriyama, Yoshinori ; Omote, Hiroshi. / Characterization of the human MATE2 proton-coupled polyspecific organic cation exporter. In: International Journal of Biochemistry and Cell Biology. 2011 ; Vol. 43, No. 6. pp. 913-918.
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