The monocarboxylate transporter family—Structure and functional characterization

@article{Halestrap2012TheMT,
  title={The monocarboxylate transporter family—Structure and functional characterization},
  author={Andrew P. Halestrap},
  journal={IUBMB Life},
  year={2012},
  volume={64}
}
  • A. Halestrap
  • Published 1 January 2012
  • Biology, Medicine
  • IUBMB Life
Monocarboxylate transporters (MCTs) catalyze the proton-linked transport of monocarboxylates such as L-lactate, pyruvate, and the ketone bodies across the plasma membrane. [...] Key Result MCTs were predicted to have 12 transmembrane helices (TMs) with intracellular C- and N-termini and a large intracellular loop between TMs 6 and 7, and this was confirmed by labeling studies and proteolytic digestion.Expand
Membrane-anchored carbonic anhydrase IV interacts with monocarboxylate transporters via their chaperones CD147 and GP70
TLDR
The results suggest that the CAIV-mediated increase in MCT transport activity requires direct binding between CAIV–His-88 and a charged amino acid in the extracellular domain of the transporter's chaperone. Expand
The SLC16A family of monocarboxylate transporters (MCTs)--physiology and function in cellular metabolism, pH homeostasis, and fluid transport.
TLDR
A comprehensive review of MCTs 1-4 is provided, linking their cellular distribution to their functions in various parts of the human body, so that the authors can better understand the physiological roles of M CTs at the systemic level. Expand
Monocarboxylic acid transport.
TLDR
Some disease states are associated with modulation of plasma membrane and mitochondrial monocarboxylate transport and MCTs are promising drug targets for cancer chemotherapy and may also be involved in drug uptake from the intestine and subsequent transport across the blood brain barrier. Expand
Identification of the essential extracellular aspartic acids conserved in human monocarboxylate transporters 1, 2, and 4.
TLDR
It is suggested that the extracellular aspartic acids conserved in hMCT1, 2, and 4 played important roles in transport activity and pH dependency, and can function as a first step of substrate and H+ recognition and transport from the extacellular to the intracellular region. Expand
The Monocarboxylate Transporter Inhibitor α-Cyano-4-Hydroxycinnamic Acid Disrupts Rat Lung Branching
TLDR
The findings show that all the biomarkers are differently expressed during fetal lung development and that CHC appears to have an inhibitory effect on lung branching and viability, in a dose dependent way. Expand
The SLC16 gene family - structure, role and regulation in health and disease.
  • A. Halestrap
  • Biology, Medicine
  • Molecular aspects of medicine
  • 2013
TLDR
It is suggested that the development of other drugs specifically targeting different MCT isoforms may provide a novel approach to cancer chemotherapy. Expand
Monocarboxylate transporters as targets and mediators in cancer therapy response.
TLDR
MCTs can act as "Trojan horses", as their elevated expression in cancer cells can mediate the entry of this chemotherapeutic agent into the cells and selectively kill cancer cells, and their expression can be used as a molecular marker to predict response to chemotherapy. Expand
Monocarboxylate Transporters (SLC16): Function, Regulation, and Role in Health and Disease
TLDR
A summary of the current literature focusing on the characterization, function, and regulation of the MCT family isoforms and on their roles in drug disposition and in health and disease is provided. Expand
Cellular distributions of monocarboxylate transporters: a review.
TLDR
The immunohistochemical localization of SMCTs and major MCT subtypes throughout the mammalian body is reviewed to reveal the metabolism and functional significance of monocarboxylates and MCTs together with the expressed intensities holds great importance. Expand
Monocarboxylate transporters in the brain and in cancer☆
TLDR
Because MCTs gate the activities of lactate, drugs targeting these transporters have been developed that could constitute new anticancer treatments and are part of a Special Issue entitled: Mitochondrial Channels. Expand
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References

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The SLC16 monocaboxylate transporter family
TLDR
The MCT proteins have the typical twelve transmembrane-spanning domain (TMD) topology of membrane transporter proteins, and their structure–function relationship is discussed, especially in relation to the future impact of the single nucleotide polymorphism (SNP) databases and, given their ability to transport pharmacologically relevant compounds, the potential impact for pharmacogenomics. Expand
The SLC16 monocaboxylate transporter family.
TLDR
The MCT proteins have the typical twelve transmembrane-spanning domain (TMD) topology of membrane transporter proteins, and their structure-function relationship is discussed, especially in relation to the future impact of the single nucleotide polymorphism (SNP) databases and, given their ability to transport pharmacologically relevant compounds, the potential impact for pharmacogenomics. Expand
The SLC16 gene family—from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond
The monocarboxylate cotransporter (MCT) family now comprises 14 members, of which only the first four (MCT1–MCT4) have been demonstrated experimentally to catalyse the proton-linked transport ofExpand
The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation.
TLDR
There is still much work to be done to characterize the properties of the different MCT isoforms and their regulation, which may have wide-ranging implications for health and disease. Expand
The monocarboxylate transporter family—Role and regulation
TLDR
The recent discovery of potent and specific MCT1 inhibitors that prevent proliferation of T‐lymphocytes confirms that MCTs may be promising pharmacological targets including for cancer chemotherapy. Expand
The loop between helix 4 and helix 5 in the monocarboxylate transporter MCT1 is important for substrate selection and protein stability.
Transport of lactate, pyruvate and the ketone bodies acetoacetate and beta-hydroxybutyrate, is mediated in most mammalian cells by members of the monocarboxylate transporter family (SLC16). AExpand
Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: Implications for the Cori cycle
TLDR
The cloning of a cDNA encoding MCT1, a monocarboxylate transporter whose properties resemble those of the erythrocyte MCT, including proton symport, trans acceleration, and sensitivity to alpha-cyanocinnammates is reported. Expand
Characterisation of human monocarboxylate transporter 4 substantiates its role in lactic acid efflux from skeletal muscle
TLDR
The characterisation of MCT4 expressed in Xenopus oocytes shows that the protein was correctly targeted to the plasma membrane and rates of substrate transport were determined from the rate of intracellular acidification monitored with the pH‐sensitive dye 2′,7′‐bis‐( carboxyethyl)‐5(6)‐carboxyfluorescein (BCECF). Expand
The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells.
TLDR
Rat MCT4 was identified as the major isoform of white muscle cells, mediating lactate efflux out of glycolytically active myocytes and was sensitive to inhibition by the thiol reagent p-chloromercuribenzoesulphonic acid. Expand
Identification of Monocarboxylate Transporter 8 as a Specific Thyroid Hormone Transporter*
TLDR
Cloned rat MCT8 was identified as a very active and specific thyroid hormone transporter and showed high expression in liver, kidney, brain, and heart. Expand
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