Functional coupling of organic anion transporter OAT10 (SLC22A13) and monocarboxylate transporter MCT1 (SLC16A1) influencing the transport function of OAT10
OAT10 (SLC22A13) is a transporter highly expressed in renal tubules and transporting organic anions including nicotinate, β-hydroxybutyrate, p-aminohippurate, and orotate. In transport assays using Xenopus oocytes and HEK293 cells, we found that apparent substrate selectivity of OAT10 was different...
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Elsevier
2022-09-01
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| Series: | Journal of Pharmacological Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861322000482 |
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| author | Naoko Ohtsu Ryuichi Ohgaki Chunhuan Jin Minhui Xu Hiroki Okanishi Ryo Takahashi Akiko Matsui Wataru Kishimoto Naoki Ishiguro Yoshikatsu Kanai |
| author_facet | Naoko Ohtsu Ryuichi Ohgaki Chunhuan Jin Minhui Xu Hiroki Okanishi Ryo Takahashi Akiko Matsui Wataru Kishimoto Naoki Ishiguro Yoshikatsu Kanai |
| author_sort | Naoko Ohtsu |
| collection | DOAJ |
| description | OAT10 (SLC22A13) is a transporter highly expressed in renal tubules and transporting organic anions including nicotinate, β-hydroxybutyrate, p-aminohippurate, and orotate. In transport assays using Xenopus oocytes and HEK293 cells, we found that apparent substrate selectivity of OAT10 was different between the expression systems, particularly less pronounced uptake of β-hydroxybutyrate in HEK293 cells. Because functional coupling between transporters may interfere with functional properties of the transporter, we searched for endogenous transporters in HEK293 cells that could affect OAT10. By means of comprehensive approach with co-immunoprecipitation followed by LC-MS/MS analysis, we identified monocarboxylate transporter MCT1 (SLC16A1) as physically coupled with OAT10. The knockdown of MCT1 in OAT10-expressing HEK293 cells increased the uptake of β-hydroxybutyrate and nicotinate, common substrates of OAT10 and MCT1, whereas the uptake of orotate, a substrate of only OAT10, was not affected. MCT1 is supposed to act as an escape route and mediate the efflux of nicotinate and β-hydroxybutyrate taken up by OAT10 localized nearby MCT1, as suggested by co-immunoprecipitation. This functional coupling would explain altered apparent substrate selectivity in HEK293 cells compared with Xenopus oocytes. The findings in this study warn in transporter studies that the expression system can interfere with assessing correct transport properties due to unexpected interactions with endogenous transporters. |
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| id | doaj.art-32976239a6174a51b67a5d310cce6df2 |
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| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-10T20:39:44Z |
| publishDate | 2022-09-01 |
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| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-32976239a6174a51b67a5d310cce6df22022-12-22T01:34:24ZengElsevierJournal of Pharmacological Sciences1347-86132022-09-0115014148Functional coupling of organic anion transporter OAT10 (SLC22A13) and monocarboxylate transporter MCT1 (SLC16A1) influencing the transport function of OAT10Naoko Ohtsu0Ryuichi Ohgaki1Chunhuan Jin2Minhui Xu3Hiroki Okanishi4Ryo Takahashi5Akiko Matsui6Wataru Kishimoto7Naoki Ishiguro8Yoshikatsu Kanai9Department of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan; Pharmacokinetics and Non-Clinical Safety Department, Nippon Boehringer Ingelheim Co., Ltd., 6-7-5 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, JapanDepartment of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, JapanPharmacokinetics and Non-Clinical Safety Department, Nippon Boehringer Ingelheim Co., Ltd., 6-7-5 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, JapanPharmacokinetics and Non-Clinical Safety Department, Nippon Boehringer Ingelheim Co., Ltd., 6-7-5 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, JapanPharmacokinetics and Non-Clinical Safety Department, Nippon Boehringer Ingelheim Co., Ltd., 6-7-5 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, JapanPharmacokinetics and Non-Clinical Safety Department, Nippon Boehringer Ingelheim Co., Ltd., 6-7-5 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, JapanDepartment of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan; Corresponding author. Department of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.OAT10 (SLC22A13) is a transporter highly expressed in renal tubules and transporting organic anions including nicotinate, β-hydroxybutyrate, p-aminohippurate, and orotate. In transport assays using Xenopus oocytes and HEK293 cells, we found that apparent substrate selectivity of OAT10 was different between the expression systems, particularly less pronounced uptake of β-hydroxybutyrate in HEK293 cells. Because functional coupling between transporters may interfere with functional properties of the transporter, we searched for endogenous transporters in HEK293 cells that could affect OAT10. By means of comprehensive approach with co-immunoprecipitation followed by LC-MS/MS analysis, we identified monocarboxylate transporter MCT1 (SLC16A1) as physically coupled with OAT10. The knockdown of MCT1 in OAT10-expressing HEK293 cells increased the uptake of β-hydroxybutyrate and nicotinate, common substrates of OAT10 and MCT1, whereas the uptake of orotate, a substrate of only OAT10, was not affected. MCT1 is supposed to act as an escape route and mediate the efflux of nicotinate and β-hydroxybutyrate taken up by OAT10 localized nearby MCT1, as suggested by co-immunoprecipitation. This functional coupling would explain altered apparent substrate selectivity in HEK293 cells compared with Xenopus oocytes. The findings in this study warn in transporter studies that the expression system can interfere with assessing correct transport properties due to unexpected interactions with endogenous transporters.http://www.sciencedirect.com/science/article/pii/S1347861322000482Organic anionMonocarboxylateTransporterFunctional couplingExogenous expression system |
| spellingShingle | Naoko Ohtsu Ryuichi Ohgaki Chunhuan Jin Minhui Xu Hiroki Okanishi Ryo Takahashi Akiko Matsui Wataru Kishimoto Naoki Ishiguro Yoshikatsu Kanai Functional coupling of organic anion transporter OAT10 (SLC22A13) and monocarboxylate transporter MCT1 (SLC16A1) influencing the transport function of OAT10 Journal of Pharmacological Sciences Organic anion Monocarboxylate Transporter Functional coupling Exogenous expression system |
| title | Functional coupling of organic anion transporter OAT10 (SLC22A13) and monocarboxylate transporter MCT1 (SLC16A1) influencing the transport function of OAT10 |
| title_full | Functional coupling of organic anion transporter OAT10 (SLC22A13) and monocarboxylate transporter MCT1 (SLC16A1) influencing the transport function of OAT10 |
| title_fullStr | Functional coupling of organic anion transporter OAT10 (SLC22A13) and monocarboxylate transporter MCT1 (SLC16A1) influencing the transport function of OAT10 |
| title_full_unstemmed | Functional coupling of organic anion transporter OAT10 (SLC22A13) and monocarboxylate transporter MCT1 (SLC16A1) influencing the transport function of OAT10 |
| title_short | Functional coupling of organic anion transporter OAT10 (SLC22A13) and monocarboxylate transporter MCT1 (SLC16A1) influencing the transport function of OAT10 |
| title_sort | functional coupling of organic anion transporter oat10 slc22a13 and monocarboxylate transporter mct1 slc16a1 influencing the transport function of oat10 |
| topic | Organic anion Monocarboxylate Transporter Functional coupling Exogenous expression system |
| url | http://www.sciencedirect.com/science/article/pii/S1347861322000482 |
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