Molecular characteristic analysis of single-nucleotide polymorphisms in SLC16A9/hMCT9

Yamaguchi, Atsushi; Mukai, Yuto; Sakuma, Tomoya; Suganuma, Yudai; Furugen, Ayako; Narumi, Katsuya; Kobayashi, Masaki

Molecular characteristic analysis of single-nucleotide polymorphisms in SLC16A9/hMCT9

Yamaguchi, Atsushi; Mukai, Yuto; Sakuma, Tomoya et al.

Life sciences, 2023, 334, 122205

Permalink : https://hdl.handle.net/2115/94050

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アクセス権	open access
URI	https://hdl.handle.net/2115/94050
タイトル	Molecular characteristic analysis of single-nucleotide polymorphisms in SLC16A9/hMCT9
著者	Yamaguchi, Atsushi ; Mukai, Yuto ; Sakuma, Tomoya ; Suganuma, Yudai ; Furugen, Ayako ; Narumi, Katsuya ; Kobayashi, Masaki
著者名 Yamaguchi, Atsushi
著者名 Mukai, Yuto
著者名 Sakuma, Tomoya
著者名 Suganuma, Yudai
e-Rad_Researcher 90767261 著者名 Furugen, Ayako
e-Rad_Researcher 90746752 著者名 Narumi, Katsuya
e-Rad_Researcher 70431319 著者名 Kobayashi, Masaki
言語	英語
キーワード	Monocarboxylate transporter 9
	Uric acid
	Creatine
	Single-nucleotide polymorphism
	Xenopus laevis oocyte
	SLC16A9
発行日	2023-12-01
出版者	Elsevier
収録物名	Life sciences
巻(号)	334
ページ	122205
抄録	Aims: Human monocarboxylate transporter 9 (hMCT9), encoded by SLC16A9, is a transporter that mediates creatine transport across the transmembrane. Previously, we reported that hMCT9 is an extracellular pH- and Na+-sensitive creatine transporter with two kinetic components. Recently, some variants of hMCT9 have been found to be associated with serum uric acid levels, hyperuricemia, and gout. Among these, two single-nucleotide polymorphisms (SNPs) have also been reported: rs550527563 (L93M) and rs2242206 (T258K). However, the effect of these SNPs on hMCT9 transport activity remains unclear.This study aimed to determine the influence of hMCT9 L93M and T258K on transport characteristics. Main methods: hMCT9 L93M and T258K were constructed by site-directed mutagenesis and expressed in Xenopus laevis oocyte. Transport activity of uric acid and creatine via hMCT9 were measured by using a Xenopus laevis oocyte heterologous expression system.Key findings: We assessed the transport activity of uric acid and creatine, and observed that hMCT9-expressing oocytes transported uric acid approximately 3- to 4-fold more than water-injected oocytes. hMCT9 L93M slightly reduced the transport activity of creatine, whereas hMCT9 T258K did not affect the transport activity. Interestingly, hMCT9 T258K abolished Na+ sensitivity and altered the substrate affinity from two components to one.Significance: In conclusion, hMCT9 SNPs affect transport activity and characteristics. hMCT9 L93M and T258K may induce dysfunction and contribute to pathologies such as hyperuricemia and gout. This is a first study to evaluate molecular characteristics of hMCT9 SNPs.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	©2023. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0024-3205
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.lfs.2023.122205