The Journal of Physiological Sciences

, Volume 69, Issue 4, pp 635–642 | Cite as

Sodium-coupled monocarboxylate transporter 1 interacts with the RING finger- and PDZ domain-containing protein PDZRN3

  • Yusuke Otsuka
  • Tomomi Furihata
  • Kiyoshi Nakagawa
  • Yuta Ohno
  • Yoshie Reien
  • Motoshi Ouchi
  • Hidefumi Wakashin
  • Shuichi Tsuruoka
  • Naohiko AnzaiEmail author
Original Paper


Sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8) mediates monocarboxylate transport in the proximal tubule of the kidney. We have identified PDZK1 and PDZ domain-containing RING finger 3 (PDZRN3) as potent binding partners of SMCT1, which has a PDZ motif (Thr–Arg–Leu), by yeast two-hybrid screening and revealed that PDZK1 enhances the transport activity of SMCT1. In this study, we aimed to characterize the interaction between SMCT1 and PDZRN3 as well as to examine how PDZRN3 regulates SMCT1 function. An interaction between SMCT1 and PDZRN3 through the PDZ motif was observed in a co-immunoprecipitation assay and yeast two-hybrid assay. A transport assay showed that PDZRN3 abolished the enhancing effect of PDZK1 on nicotinate uptake via SMCT1. Our results suggest that SMCT1 interacts with PDZRN3 and that PDZRN3 may regulate SMCT1 function by interfering with the interaction between SMCT1 and PDZK1.


SMCT1 PDZRN3 Monocarboxylate Transporter PDZ protein 



The authors would like to thank Asuka Morita and Masakatsu Nohara for their assistance in experiments. This work was supported in part by grants from the Japan Society for the Promotion of Science (KAKENHI 15590233, 18590900, 21390073, 26461258, 18K08200), Strategic Research Foundation Grant-aided Project for Private Universities (S1412001), The Nakatomi Foundation (2005, 2010), Gout Research Foundation of Japan (2008, 2009, 2010, 2011, 2012, 2013, 2015, 2016, 2017), Takeda Science Foundation (2007), the Salt Science Research Foundation (No. 0524, 0721), and Shimabara Foundation (2006, 2007, 2013) to NA.

Author contributions

NA designed the study. YO, YO and NA performed Y2H. NA, YR and KN checked and confirmed the experimental materials and data used in this study. YO, YO and MO performed transport assay. YO, YR, TF and HW performed biochemical and immunohistochemical analysis. YO, TF and NA wrote the manuscript. All authors discussed the results and commented on the manuscript.

Compliance with ethical standards

Conflict of interest

All authors of this manuscript declare that we have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

12576_2019_681_MOESM1_ESM.docx (847 kb)
Supplementary file1 (DOCX 847 kb)


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Copyright information

© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PharmacologyChiba University Graduate School of MedicineChibaJapan
  2. 2.Department of Pharmacology and ToxicologyDokkyo Medical University School of MedicineTochigiJapan
  3. 3.Department of Nephrology, Graduate School of MedicineNippon Medical SchoolTokyoJapan

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