Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells.
Dimmer KS
,
Friedrich B
,
Lang F
,
Deitmer JW
,
Bröer S
.
???displayArticle.abstract???
Transport of lactate and other monocarboxylates in mammalian cells is mediated by a family of transporters, designated monocarboxylate transporters (MCTs). The MCT4 member of this family has recently been identified as the major isoform of white muscle cells, mediating lactate efflux out of glycolytically active myocytes [Wilson, Jackson, Heddle, Price, Pilegaard, Juel, Bonen, Montgomery, Hutter and Halestrap (1998) J. Biol. Chem. 273, 15920-15926]. To analyse the functional properties of this transporter, rat MCT4 was expressed in Xenopus laevis oocytes and transport activity was monitored by flux measurements with radioactive tracers and by changes of the cytosolic pH using pH-sensitive microelectrodes. Similar to other members of this family, monocarboxylate transport via MCT4 is accompanied by the transport of H(+) across the plasma membrane. Uptake of lactate strongly increased with decreasing extracellular pH, which resulted from a concomitant drop in the K(m) value. MCT4 could be distinguished from the other isoforms mainly in two respects. First, MCT4 is a low-affinity MCT: for L-lactate K(m) values of 17+/-3 mM (pH-electrode) and 34+/-5 mM (flux measurements with L-[U-(14)C]lactate) were determined. Secondly, lactate is the preferred substrate of MCT4. K(m) values of other monocarboxylates were either similar to the K(m) value for lactate (pyruvate, 2-oxoisohexanoate, 2-oxoisopentanoate, acetoacetate) or displayed much lower affinity for the transporter (beta-hydroxybutyrate and short-chain fatty acids). Under physiological conditions, rat MCT will therefore preferentially transport lactate. Monocarboxylate transport via MCT4 could be competitively inhibited by alpha-cyano-4-hydroxycinnamate, phloretin and partly by 4, 4'-di-isothiocyanostilbene-2,2'-disulphonic acid. Similar to MCT1, monocarboxylate transport via MCT4 was sensitive to inhibition by the thiol reagent p-chloromercuribenzoesulphonic acid.
Bröer,
Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes.
1999, Pubmed,
Xenbase
Bröer,
Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes.
1999,
Pubmed
,
Xenbase
Bröer,
The astroglial ASCT2 amino acid transporter as a mediator of glutamine efflux.
1999,
Pubmed
,
Xenbase
Bröer,
Expression of Na+-independent isoleucine transport activity from rat brain in Xenopus laevis oocytes.
1994,
Pubmed
,
Xenbase
Bröer,
Comparison of lactate transport in astroglial cells and monocarboxylate transporter 1 (MCT 1) expressing Xenopus laevis oocytes. Expression of two different monocarboxylate transporters in astroglial cells and neurons.
1997,
Pubmed
,
Xenbase
Bröer,
Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH.
1998,
Pubmed
,
Xenbase
Carpenter,
The kinetics, substrate and inhibitor specificity of the lactate transporter of Ehrlich-Lettre tumour cells studied with the intracellular pH indicator BCECF.
1994,
Pubmed
Chomczynski,
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
1987,
Pubmed
De Bruijne,
Kinetic analysis of L-lactate transport in human erythrocytes via the monocarboxylate-specific carrier system.
1983,
Pubmed
Deitmer,
Electrogenic sodium-dependent bicarbonate secretion by glial cells of the leech central nervous system.
1991,
Pubmed
Deuticke,
Monocarboxylate transport in erythrocytes.
1982,
Pubmed
Doi,
Extracellular K+ and intracellular pH allosterically regulate renal Kir1.1 channels.
1996,
Pubmed
,
Xenbase
Eladari,
Polarized expression of different monocarboxylate transporters in rat medullary thick limbs of Henle.
1999,
Pubmed
Garcia,
Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle.
1994,
Pubmed
Garcia,
cDNA cloning of MCT2, a second monocarboxylate transporter expressed in different cells than MCT1.
1995,
Pubmed
Gerhart,
Expression of the monocarboxylate transporter MCT2 by rat brain glia.
1998,
Pubmed
Gerhart,
Distribution of monocarboxylate transporters MCT1 and MCT2 in rat retina.
1999,
Pubmed
Halestrap,
The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation.
1999,
Pubmed
,
Xenbase
Hamprecht,
Primary glial cultures as a model for studying hormone action.
1985,
Pubmed
Jackson,
The kinetics, substrate, and inhibitor specificity of the monocarboxylate (lactate) transporter of rat liver cells determined using the fluorescent intracellular pH indicator, 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein.
1996,
Pubmed
Juel,
Muscle lactate transport studied in sarcolemmal giant vesicles.
1991,
Pubmed
Koehler-Stec,
Monocarboxylate transporter expression in mouse brain.
1998,
Pubmed
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Löffner,
Immunocytochemical characterization of neuron-rich primary cultures of embryonic rat brain cells by established neuronal and glial markers and by monospecific antisera against cyclic nucleotide-dependent protein kinases and the synaptic vesicle protein synapsin I.
1986,
Pubmed
Munsch,
Sodium-bicarbonate cotransport current in identified leech glial cells.
1994,
Pubmed
Nedergaard,
Carrier-mediated transport of lactic acid in cultured neurons and astrocytes.
1993,
Pubmed
Pellerin,
Expression of monocarboxylate transporter mRNAs in mouse brain: support for a distinct role of lactate as an energy substrate for the neonatal vs. adult brain.
1998,
Pubmed
Poitry-Yamate,
Lactate released by Müller glial cells is metabolized by photoreceptors from mammalian retina.
1995,
Pubmed
Price,
Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past.
1998,
Pubmed
Rahman,
Helix 8 and helix 10 are involved in substrate recognition in the rat monocarboxylate transporter MCT1.
1999,
Pubmed
,
Xenbase
Wang,
Kinetics of the sarcolemmal lactate carrier in single heart cells using BCECF to measure pHi.
1994,
Pubmed
Wang,
Substrate and inhibitor specificities of the monocarboxylate transporters of single rat heart cells.
1996,
Pubmed
Wibrand,
Reconstitution of the lactate carrier from rat skeletal-muscle sarcolemma.
1994,
Pubmed
Wilson,
Lactic acid efflux from white skeletal muscle is catalyzed by the monocarboxylate transporter isoform MCT3.
1998,
Pubmed
Yoon,
Identification of a unique monocarboxylate transporter (MCT3) in retinal pigment epithelium.
1997,
Pubmed
von Grumbckow,
Kinetics of lactate and pyruvate transport in cultured rat myotubes.
1999,
Pubmed
