Interaction of carbonic anhydrases with lactate-transporting MCTs

Abstract

Event Abstract Back to Event Interaction of carbonic anhydrases with lactate-transporting MCTs Joachim W. Deitmer1*, Michael Klier1 and Holger M. Becker1 1 University of Kaisersautern, General Zoology, Germany Background and aim. Carbonic anhydrases (CAs) have not only been identified as ubiquitous enzymes catalyzing the fast reversible hydration of carbon dioxide to generate or consume protons and bicarbonate, but also as intra- and extracellular proteins, which facilitate transport function of acid/base transporting membrane proteins. Functional interactions between CAs and acid/base transporters, such as chloride/bicarbonate exchanger (AE), sodium-bicarbonate cotransporter (NBC) and sodium/hydrogen exchanger (NHE) have been reported, which appear to require both catalytic CA activity as well as direct binding of the enzyme to specific sites on the transporter. In contrast, functional interaction between different CA isoforms and lactate-proton-cotransporting monocarboxylate transporters (MCTs) has been found to be isoform-specific and independent of CA catalytic activity (1, 2). MCTs play a crucial role in the shuttling of lactate between glycolytic and oxidative cell types in different tissues like muscle and brain, and may also play a role in removing acid from cells. Methods. We have used Xenopus laevis oocytes as heterologous expression system to study MCTs and CA alone and when expressed together, and used H+-sensitive microelectrode and mass spectrometry to determine transporter and enzyme activity. Results. Our studies on the interaction between different CA isoforms, including CAIX, which is up-regulated in hypoxic/cancerous tissues, and MCT isoforms 1, 2, and 4 in Xenopus oocytes will be summarized and imbedded into a scheme which links H+ fluxes, CA and MCT expression with metabolic processes. In particular, CAs may act as H+-collecting antennae (3), which counteract the dissipation of the transmembrane H+ gradient driving the cotransport with lactate via MCTs. Conclusions. It is concluded that membrane transporters may directly interact with intracellular and extracellular carbonic anhydrases, leading to functional changes in transport activity, which may be relevant in particular in hypoxic cells and tissues. Acknowledgements Supported by grants from the Deutsche Forschungsgemeinschaft and the Landesschwerpunkt RIMP. References (1) Becker, H.M. and Deitmer, J.W. (2008) J. Biol. Chem. 283, 21655-67. (2) Klier, M. et al. (2011) J. Biol. Chem. 286, 27781-91. (3) Becker, H.M. et al. (2011) Proc Natl. Acad. Sci. U.S.A. 108, 3071-3076. Keywords: pH, Lactate, monocarboxylate transporter, CAIX, Xenopus oocyte Conference: 4th Annual Meeting of the International Society of Proton Dynamics in Cancer, Garching, Germany, 10 Oct - 12 Oct, 2013. Presentation Type: Abstract Topic: 3. pH, cell signalling and growth Citation: Deitmer JW, Klier M and Becker HM (2014). Interaction of carbonic anhydrases with lactate-transporting MCTs. Front. Pharmacol. Conference Abstract: 4th Annual Meeting of the International Society of Proton Dynamics in Cancer. doi: 10.3389/conf.fphar.2014.61.00017 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 17 Dec 2013; Published Online: 07 Feb 2014. * Correspondence: Prof. Joachim W Deitmer, University of Kaisersautern, General Zoology, Kaiserslautern, Rheinland-Pfalz, D-67663, Germany, deitmer@biologie.uni-kl.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Joachim W Deitmer Michael Klier Holger M Becker Google Joachim W Deitmer Michael Klier Holger M Becker Google Scholar Joachim W Deitmer Michael Klier Holger M Becker PubMed Joachim W Deitmer Michael Klier Holger M Becker Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.