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Involvement of Histidine Residue His382 in pH Regulation of MCT4 Activity
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| Title: | Involvement of Histidine Residue His382 in pH Regulation of MCT4 Activity |
| Authors: | Sasaki, Shotaro Browse this author | | Kobayashi, Masaki Browse this author →KAKEN DB | | Futagi, Yuya Browse this author | | Ogura, Jiro Browse this author →KAKEN DB | | Yamaguchi, Hiroaki Browse this author →KAKEN DB | | Iseki, Ken Browse this author →KAKEN DB |
| Issue Date: | 28-Apr-2015 |
| Publisher: | PLOS |
| Journal Title: | PLOS ONE |
| Volume: | 10 |
| Issue: | 4 |
| Start Page: | e0122738 |
| Publisher DOI: | 10.1371/journal.pone.0122738 |
| Abstract: | 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. |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/59505 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 井関 健
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