A surface proton antenna in carbonic anhydrase II supports lactate transport in cancer cells
- University of Kaiserslautern, Germany
Abstract
Many tumor cells produce vast amounts of lactate and acid, which have to be removed from the cell to avoid intracellular lactacidosis and suffocation of metabolism. In the present study, we show that proton-driven lactate flux is enhanced by the intracellular carbonic anhydrase CAII, which is colocalized with the monocarboxylate transporter MCT1 in MCF-7 breast cancer cells. Co-expression of MCTs with various CAII mutants in Xenopus oocytes demonstrated that CAII facilitates MCT transport activity via CAII-Glu69 and CAII-Asp72, which could function as surface proton antennae for the enzyme. While CAII-Glu69 and CAII-Asp72 seem to mediate proton transfer between enzyme and transporter, CAII-His64, the central residue of the enzyme's intramolecular proton shuttle, is not involved in proton shuttling between the two proteins, but mediates binding between MCT and CAII. Taken together, the results suggest that CAII features a moiety that exclusively mediates proton exchange with the MCT to facilitate transport activity.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1-9.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (BE 4310/6-1)
- Holger M Becker
Stiftung Rheinland-Pfalz für Innovation (961-386261/957)
- Holger M Becker
Research Initiative BioComp
- Joachim W Deitmer
- Holger M Becker
Landesschwerpunkt Membrantransport
- Joachim W Deitmer
- Holger M Becker
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: The procedure of removing oocytes from Xenopus laevis females was approved by the Landesuntersuchungsamt Rheinland-Pfalz, Koblenz (23 177-07/A07-2-003 {section sign}6) and the Niedersächsisches Landesamt für Verbraucherschutz und Lebensmittelsicherheit, Oldenburg (33.19-42502-05-17A113).
Copyright
© 2018, Noor et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A surface proton antenna in carbonic anhydrase II supports lactate transport in cancer cells
eLife 7:e35176.
https://doi.org/10.7554/eLife.35176
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