Sodium-coupled monocarboxylate transporter 1 interacts with the RING finger- and PDZ domain-containing protein PDZRN3
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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.
KeywordsSMCT1 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.
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.
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Conflict of interest
All authors of this manuscript declare that we have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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