title: Intracellular and extracellular carbonic anhydrases cooperate non-enzymatically to enhance activity of monocarboxylate transporters.
abstract: 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.
authors: From the Division of General Zoology, Department of Biology, University of Kaiserslautern D-67653 Kaiserslautern, Germany and.
authors: Michael
authors: M
authors: Klier
authors: Fabian T
authors: FT
authors: Andes
authors: Joachim W
authors: JW
authors: Deitmer
authors: Holger M
authors: HM
authors: Becker
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D024402:Carbonic Anhydrase II / Q000378:metabolism; D030741:Carbonic Anhydrase IV / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007657:Ketone Bodies / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology; D010103:Oxygen Isotopes / Q000493:pharmacokinetics; D019289:Pyruvic Acid / Q000378:metabolism*; D051381:Rats; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D024402:Carbonic Anhydrase II; D030741:Carbonic Anhydrase IV; D007657:Ketone Bodies; D019344:Lactic Acid; D008565:Membrane Proteins; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D010103:Oxygen Isotopes; D019289:Pyruvic Acid; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C406962:SLC16A4 protein, human; C548247:CA4 protein, human
keywords: Ion-sensitive Electrodes; Lactic Acid; Protein Complexes; Protein Expression; Proton-collecting Antenna; Transport Metabolon; Xenopus Oocytes; pH Regulation