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J Biol Chem
2011 Aug 05;28631:27781-91. doi: 10.1074/jbc.M111.255331.
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Transport activity of the high-affinity monocarboxylate transporter MCT2 is enhanced by extracellular carbonic anhydrase IV but not by intracellular carbonic anhydrase II.
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The ubiquitous enzyme carbonic anhydrase isoform II (CAII) has been shown to enhance transport activity of the proton-coupled monocarboxylate transporters MCT1 and MCT4 in a non-catalytic manner. In this study, we investigated the role of cytosolic CAII and of the extracellular, membrane-bound CA isoform IV (CAIV) on the lactate transport activity of the high-affinity monocarboxylate transporter MCT2, heterologously expressed in Xenopus oocytes. In contrast to MCT1 and MCT4, transport activity of MCT2 was not altered by CAII. However, coexpression of CAIV with MCT2 resulted in a significant increase in MCT2 transport activity when the transporter was coexpressed with its associated ancillary protein GP70 (embigin). The CAIV-mediated augmentation of MCT2 activity was independent of the catalytic activity of the enzyme, as application of the CA-inhibitor ethoxyzolamide or coexpressing the catalytically inactive mutant CAIV-V165Y did not suppress CAIV-mediated augmentation of MCT2 transport activity. Furthermore, exchange of His-88, mediating an intramolecular H(+)-shuttle in CAIV, to alanine resulted only in a slight decrease in CAIV-mediated augmentation of MCT2 activity. The data suggest that extracellular membrane-bound CAIV, but not cytosolic CAII, augments transport activity of MCT2 in a non-catalytic manner, possibly by facilitating a proton pathway other than His-88.
Alvarez,
Direct extracellular interaction between carbonic anhydrase IV and the human NBC1 sodium/bicarbonate co-transporter.
2003, Pubmed
Alvarez,
Direct extracellular interaction between carbonic anhydrase IV and the human NBC1 sodium/bicarbonate co-transporter.
2003,
Pubmed Badger,
Carbonic Anhydrase Activity Associated with the Cyanobacterium Synechococcus PCC7942.
1989,
Pubmed Becker,
Transport activity of MCT1 expressed in Xenopus oocytes is increased by interaction with carbonic anhydrase.
2005,
Pubmed
,
Xenbase Becker,
Nonenzymatic augmentation of lactate transport via monocarboxylate transporter isoform 4 by carbonic anhydrase II.
2010,
Pubmed
,
Xenbase Becker,
Facilitated lactate transport by MCT1 when coexpressed with the sodium bicarbonate cotransporter (NBC) in Xenopus oocytes.
2004,
Pubmed
,
Xenbase Becker,
Carbonic anhydrase II increases the activity of the human electrogenic Na+/HCO3- cotransporter.
2007,
Pubmed
,
Xenbase Becker,
Intramolecular proton shuttle supports not only catalytic but also noncatalytic function of carbonic anhydrase II.
2011,
Pubmed
,
Xenbase Becker,
Nonenzymatic proton handling by carbonic anhydrase II during H+-lactate cotransport via monocarboxylate transporter 1.
2008,
Pubmed
,
Xenbase Bergersen,
A novel postsynaptic density protein: the monocarboxylate transporter MCT2 is co-localized with delta-glutamate receptors in postsynaptic densities of parallel fiber-Purkinje cell synapses.
2001,
Pubmed Bolaños,
Persistent mitochondrial damage by nitric oxide and its derivatives: neuropathological implications.
2010,
Pubmed Bröer,
Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes.
1999,
Pubmed
,
Xenbase Bröer,
Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH.
1998,
Pubmed
,
Xenbase Cammer,
Carbonic anhydrase activity in myelin from sciatic nerves of adult and young rats: quantitation and inhibitor sensitivity.
1979,
Pubmed Deitmer,
Electrogenic sodium-dependent bicarbonate secretion by glial cells of the leech central nervous system.
1991,
Pubmed Deitmer,
pH regulation and proton signalling by glial cells.
1996,
Pubmed Di Fiore,
Carbonic anhydrase inhibitors: the X-ray crystal structure of ethoxzolamide complexed to human isoform II reveals the importance of thr200 and gln92 for obtaining tight-binding inhibitors.
2008,
Pubmed Fossum,
The MRC OX-47 antigen is a member of the immunoglobulin superfamily with an unusual transmembrane sequence.
1991,
Pubmed Garcia,
cDNA cloning of MCT2, a second monocarboxylate transporter expressed in different cells than MCT1.
1995,
Pubmed Halestrap,
The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation.
1999,
Pubmed
,
Xenbase Halestrap,
The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond.
2004,
Pubmed Hallerdei,
T tubules and surface membranes provide equally effective pathways of carbonic anhydrase-facilitated lactic acid transport in skeletal muscle.
2010,
Pubmed Hurt,
Catalytic properties of murine carbonic anhydrase IV.
1997,
Pubmed Jackson,
Cloning of the monocarboxylate transporter isoform MCT2 from rat testis provides evidence that expression in tissues is species-specific and may involve post-transcriptional regulation.
1997,
Pubmed Juel,
Human skeletal muscle and erythrocyte proteins involved in acid-base homeostasis: adaptations to chronic hypoxia.
2003,
Pubmed Kirk,
CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression.
2000,
Pubmed Li,
Carbonic anhydrase II binds to and enhances activity of the Na+/H+ exchanger.
2002,
Pubmed McMurtrie,
The bicarbonate transport metabolon.
2004,
Pubmed Messonnier,
Importance of pH regulation and lactate/H+ transport capacity for work production during supramaximal exercise in humans.
2007,
Pubmed Ovens,
The inhibition of monocarboxylate transporter 2 (MCT2) by AR-C155858 is modulated by the associated ancillary protein.
2010,
Pubmed
,
Xenbase Pellerin,
Evidence supporting the existence of an activity-dependent astrocyte-neuron lactate shuttle.
1998,
Pubmed Pierre,
Monocarboxylate transporters in the central nervous system: distribution, regulation and function.
2005,
Pubmed Pushkin,
Molecular mechanism of kNBC1-carbonic anhydrase II interaction in proximal tubule cells.
2004,
Pubmed Ro,
pH microdomains in oligodendrocytes.
2004,
Pubmed Silverman,
Carbonic anhydrase: oxygen-18 exchange catalyzed by an enzyme with rate-contributing proton-transfer steps.
1982,
Pubmed Sterling,
The extracellular component of a transport metabolon. Extracellular loop 4 of the human AE1 Cl-/HCO3- exchanger binds carbonic anhydrase IV.
2002,
Pubmed Sültemeyer,
Mass Spectrometric Measurement of Intracellular Carbonic Anhydrase Activity in High and Low C(i) Cells of Chlamydomonas: Studies Using O Exchange with C/O Labeled Bicarbonate.
1990,
Pubmed Supuran,
Carbonic anhydrases as targets for medicinal chemistry.
2007,
Pubmed Svichar,
Functional demonstration of surface carbonic anhydrase IV activity on rat astrocytes.
2006,
Pubmed Svichar,
Surface carbonic anhydrase activity on astrocytes and neurons facilitates lactate transport.
2003,
Pubmed Syková,
Diffusion in brain extracellular space.
2008,
Pubmed Vaughan-Jones,
Role of bicarbonate in the regulation of intracellular pH in the mammalian ventricular myocyte.
2002,
Pubmed Vince,
Carbonic anhydrase II binds to the carboxyl terminus of human band 3, the erythrocyte C1-/HCO3- exchanger.
1998,
Pubmed Vince,
Localization of the Cl-/HCO3- anion exchanger binding site to the amino-terminal region of carbonic anhydrase II.
2000,
Pubmed Voipio,
Interstitial PCO2 and pH, and their role as chemostimulants in the isolated respiratory network of neonatal rats.
1997,
Pubmed Wetzel,
Extracellular carbonic anhydrase activity facilitates lactic acid transport in rat skeletal muscle fibres.
2001,
Pubmed Wilson,
Basigin (CD147) is the target for organomercurial inhibition of monocarboxylate transporter isoforms 1 and 4: the ancillary protein for the insensitive MCT2 is EMBIGIN (gp70).
2005,
Pubmed
,
Xenbase Wilson,
Studies on the DIDS-binding site of monocarboxylate transporter 1 suggest a homology model of the open conformation and a plausible translocation cycle.
2009,
Pubmed
,
Xenbase Wilson,
Fluorescence resonance energy transfer studies on the interaction between the lactate transporter MCT1 and CD147 provide information on the topology and stoichiometry of the complex in situ.
2002,
Pubmed
