SLC10A4 is a protease-activated transporter that transports bile acids

Takuya Abe, Yoshitomi Kanemitu, Masateru Nakasone, Ichiro Kawahata, Tohru Yamakuni, Akira Nakajima, Naoto Suzuki, Masazumi Nishikawa, Takanori Hishinuma, Yoshihisa Tomioka

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6 Citations (Scopus)

Abstract

SLC10A4 belongs to the sodium bile acid cotransporter family, but has no transport activity for bile acids. We performed multiple amino acid alignments and examined the relationships between the SLC10 proteins. The extracellular N-terminus of SLC10A4 was predicted to be relatively longer at the amino acid level than those of SLC10A1, SLC10A2 and SLC10A6. We examined the relationship between the N-terminus and transport activity of SLC10A4. Rat Slc10a4 is predominantly expressed in rat cholinergic neurons; therefore, TE671 cells expressing the acetylcholine receptor and acetylcholinesterase were used. After thrombin treatment, western blotting and immunofluorescence staining demonstrated that the N-terminus of SLC10A4 might be cleaved. Substrates were added to the cells, and their uptake was quantified by liquid chromatography tandem mass spectrometry. Lithocholic acid (LCA) and taurocholic acid (TCA) uptake and cell death effects of LCA were increased by thrombin treatment. After RNA interference treatment for SLC10A4, bile acid uptake was also quantified. In consequence, increases in the LCA and TCA uptake did not occur. Therefore, SLC10A4 may have low activity but becomes activated by proteases, including thrombin, following cleavage. We have demonstrated that SLC10A4 appears to be a protease-activated transporter and transports bile acids.

Original languageEnglish
Pages (from-to)93-101
Number of pages9
JournalJournal of biochemistry
Volume154
Issue number1
DOIs
Publication statusPublished - 2013 Jul 1

Keywords

  • bile acid
  • mass spectrometry
  • thrombin
  • transporter

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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    Abe, T., Kanemitu, Y., Nakasone, M., Kawahata, I., Yamakuni, T., Nakajima, A., Suzuki, N., Nishikawa, M., Hishinuma, T., & Tomioka, Y. (2013). SLC10A4 is a protease-activated transporter that transports bile acids. Journal of biochemistry, 154(1), 93-101. https://doi.org/10.1093/jb/mvt031