ArticlePloS one2014
Involvement of Histidine Residue His382 in pH Regulation of MCT4 Activity.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- pH-mediated activation of the lysosomal arginine sensor SLC38A9.FEBS letters · 2026Article
- Itaconate transport across the plasma membrane and Salmonella-containing vacuole via MCT1/4 modulates macrophage antibacterial activity.Nature communications · 2025Article
- pH-dependent regulation in SLC38A9.bioRxiv : the preprint server for biology · 2025Article
- Changes in morphofunctional parameters of erythrocytes and oxygen-binding capacity of hemoglobin under the influence of microorganisms of various types.European biophysics journal : EBJ · 2025Article
- Integrating zinc homeostasis network and immune landscape: a five-gene prognostic framework for precision oncology in lung adenocarcinoma.Frontiers in immunology · 2025Article
- Fibroblasts and mouse breast cancer cells can form cellular aggregates in improved soft agar culture medium.Molecular and cellular biochemistry · 2023Article
- Role of Human Monocarboxylate Transporter 1 (hMCT1) and 4 (hMCT4) in Tumor Cells and the Tumor Microenvironment.Cancer management and research · 2023Review
- Autoregulation of HBritish journal of cancer · 2022Article
- Anopheles coluzzii stearoyl-CoA desaturase is essential for adult female survival and reproduction upon blood feeding.PLoS pathogens · 2021Article
- Mycobacterium tuberculosis requires glyoxylate shunt and reverse methylcitrate cycle for lactate and pyruvate metabolism.Molecular microbiology · 2019Article
- Mechanistic basis of L-lactate transport in the SLC16 solute carrier family.Nature communications · 2019Article
- Intracranial artery stenosis: Current status of evaluation and treatment in China.Chronic diseases and translational medicine · 2017Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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