Involvement of Histidine Residue His382 in pH Regulation of MCT4 Activity

Sasaki, Shotaro; Kobayashi, Masaki; Futagi, Yuya; Ogura, Jiro; Yamaguchi, Hiroaki; Iseki, Ken

Involvement of Histidine Residue His382 in pH Regulation of MCT4 Activity

Sasaki, Shotaro; Kobayashi, Masaki; Futagi, Yuya et al.

PLOS ONE, 2015, 10(4), e0122738

Permalink : https://hdl.handle.net/2115/59505

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アクセス権	open access
URI	https://hdl.handle.net/2115/59505
タイトル	Involvement of Histidine Residue His382 in pH Regulation of MCT4 Activity
著者	Sasaki, Shotaro ; Kobayashi, Masaki ; Futagi, Yuya ; Ogura, Jiro ; Yamaguchi, Hiroaki ; Iseki, Ken
著者名 Sasaki, Shotaro
e-Rad_Researcher 70431319 著者名 Kobayashi, Masaki
著者名 Futagi, Yuya
e-Rad_Researcher 20580640 著者名 Ogura, Jiro
e-Rad_Researcher 80400373 著者名 Yamaguchi, Hiroaki
e-Rad_Researcher 40203062 著者名 Iseki, Ken
言語	英語
発行日	2015-04-28
出版者	PLOS
収録物名	PLOS ONE
巻(号)	10(4)
ページ	e0122738
抄録	Monocarboxylate transporter 4 (MCT4) is a pH-dependent bi-directional lactate transporter. Transport of lactate via MCT4 is increased by extracellular acidification. We investigated the critical histidine residue involved in pH regulation of MCT4 function. Transport of lactate via MCT4 was measured by using a Xenopus laevis oocyte expression system. MCT4-mediated lactate transport was inhibited by Zn2+ in a pH physiological condition but not in an acidic condition. The histidine modifier DEPC (diethyl pyrocarbonate) reduced MCT4 activity but did not completely inactivate MCT4. After treatment with DEPC, pH regulation of MCT4 function was completely knocked out. Inhibitory effects of DEPC were reversed by hydroxylamine and suppressed in the presence of excess lactate and Zn2+. Therefore, we performed an experiment in which the extracellular histidine residue was replaced with alanine. Consequently, the pH regulation of MCT4-H382A function was also knocked out. Our findings demonstrate that the histidine residue His382 in the extracellular loop of the transporter is essential for pH regulation of MCT4-mediated substrate transport activity.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 4.0 International
PISSN	1932-6203
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1371/journal.pone.0122738