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J Biol Chem
2014 Jan 31;2895:2765-75. doi: 10.1074/jbc.M113.537043.
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Intracellular and extracellular carbonic anhydrases cooperate non-enzymatically to enhance activity of monocarboxylate transporters.
Klier M
,
Andes FT
,
Deitmer JW
,
Becker HM
.
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Proton-coupled monocarboxylate transporters (MCTs) are carriers of high-energy metabolites such as lactate, pyruvate, and ketone bodies and are expressed in most tissues. It has previously been shown that transport activity of MCT1 and MCT4 is enhanced by the cytosolic carbonic anhydrase II (CAII) independent of its catalytic activity. We have now studied the influence of the extracellular, membrane-bound CAIV on transport activity of MCT1/4, heterologously expressed in Xenopus oocytes. Coexpression of CAIV with MCT1 and MCT4 resulted in a significant increase in MCT transport activity, even in the nominal absence of CO2/HCO3(-). CAIV-mediated augmentation of MCT activity was independent of the CAIV catalytic function, since application of the CA-inhibitor ethoxyzolamide or coexpression of the catalytically inactive mutant CAIV-V165Y did not suppress CAIV-mediated augmentation of MCT transport activity. The interaction required CAIV at the extracellular surface, since injection of CAIV protein into the oocyte cytosol did not augment MCT transport function. The effects of cytosolic CAII (injected as protein) and extracellular CAIV (expressed) on MCT transport activity, were additive. Our results suggest that intra- and extracellular carbonic anhydrases can work in concert to ensure rapid shuttling of metabolites across the cell membrane.
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
Becker,
Transport activity of MCT1 expressed in Xenopus oocytes is increased by interaction with carbonic anhydrase.
2005,
Pubmed
,
Xenbase
Becker,
Carbonic anhydrase II increases the activity of the human electrogenic Na+/HCO3- cotransporter.
2007,
Pubmed
,
Xenbase
Becker,
Nonenzymatic proton handling by carbonic anhydrase II during H+-lactate cotransport via monocarboxylate transporter 1.
2008,
Pubmed
,
Xenbase
Becker,
Intramolecular proton shuttle supports not only catalytic but also noncatalytic function of carbonic anhydrase II.
2011,
Pubmed
,
Xenbase
Becker,
Facilitated lactate transport by MCT1 when coexpressed with the sodium bicarbonate cotransporter (NBC) in Xenopus oocytes.
2004,
Pubmed
,
Xenbase
Becker,
Carbonic anhydrases and their interplay with acid/base-coupled membrane transporters.
2014,
Pubmed
,
Xenbase
Becker,
Nonenzymatic augmentation of lactate transport via monocarboxylate transporter isoform 4 by carbonic anhydrase II.
2010,
Pubmed
,
Xenbase
Bergersen,
Immunogold cytochemistry identifies specialized membrane domains for monocarboxylate transport in the central nervous system.
2002,
Pubmed
Bouzier-Sore,
Lactate is a preferential oxidative energy substrate over glucose for neurons in culture.
2003,
Pubmed
Bröer,
Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH.
1998,
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
Deitmer,
Electrogenic sodium-dependent bicarbonate secretion by glial cells of the leech central nervous system.
1991,
Pubmed
Deitmer,
Transport metabolons with carbonic anhydrases.
2013,
Pubmed
Dimmer,
The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells.
2000,
Pubmed
,
Xenbase
Ghandour,
Glial cell markers in the reeler mutant mouse: a biochemical and immunohistological study.
1981,
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
Imtaiyaz Hassan,
Structure, function and applications of carbonic anhydrase isozymes.
2013,
Pubmed
Kirk,
CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression.
2000,
Pubmed
Klier,
Transport activity of the high-affinity monocarboxylate transporter MCT2 is enhanced by extracellular carbonic anhydrase IV but not by intracellular carbonic anhydrase II.
2011,
Pubmed
,
Xenbase
Li,
A novel carbonic anhydrase II binding site regulates NHE1 activity.
2006,
Pubmed
Li,
Carbonic anhydrase II binds to and enhances activity of the Na+/H+ exchanger.
2002,
Pubmed
Magistretti,
Neurotransmitters regulate energy metabolism in astrocytes: implications for the metabolic trafficking between neural cells.
1993,
Pubmed
Maren,
Carbonic anhydrase: chemistry, physiology, and inhibition.
1967,
Pubmed
Martínez,
General requirement for harvesting antennae at ca and h channels and transporters.
2010,
Pubmed
McMurtrie,
The bicarbonate transport metabolon.
2004,
Pubmed
Nicholson,
Extracellular space structure revealed by diffusion analysis.
1998,
Pubmed
Okuyama,
Carbonic anhydrase IV: role of removal of C-terminal domain in glycosylphosphatidylinositol anchoring and realization of enzyme activity.
1995,
Pubmed
Okuyama,
Human carbonic anhydrase IV: cDNA cloning, sequence comparison, and expression in COS cell membranes.
1992,
Pubmed
Osborne,
An improved method for the purification of carbonic anhydrase isozymes by affinity chromatography.
1975,
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
Pellerin,
Cellular and subcellular distribution of monocarboxylate transporters in cultured brain cells and in the adult brain.
,
Pubmed
Pellerin,
Food for thought: the importance of glucose and other energy substrates for sustaining brain function under varying levels of activity.
2010,
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
Schneider,
GPI-anchored carbonic anhydrase IV displays both intra- and extracellular activity in cRNA-injected oocytes and in mouse neurons.
2013,
Pubmed
,
Xenbase
Silverman,
Carbonic anhydrase: oxygen-18 exchange catalyzed by an enzyme with rate-contributing proton-transfer steps.
1982,
Pubmed
Simpson,
Supply and demand in cerebral energy metabolism: the role of nutrient transporters.
2007,
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
Stridh,
Lactate flux in astrocytes is enhanced by a non-catalytic action of carbonic anhydrase II.
2012,
Pubmed
,
Xenbase
Svichar,
Functional demonstration of surface carbonic anhydrase IV activity on rat astrocytes.
2006,
Pubmed
Syková,
Diffusion in brain extracellular space.
2008,
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
Vaughan-Jones,
Intrinsic H(+) ion mobility in the rabbit ventricular myocyte.
2002,
Pubmed
Vince,
Carbonic anhydrase II binds to the carboxyl terminus of human band 3, the erythrocyte C1-/HCO3- exchanger.
1998,
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,
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
Wyss,
In vivo evidence for lactate as a neuronal energy source.
2011,
Pubmed
Zhu,
Carbonic anhydrase IV from human lung. Purification, characterization, and comparison with membrane carbonic anhydrase from human kidney.
1990,
Pubmed
