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FEBS Open Bio
2019 Jul 01;97:1204-1211. doi: 10.1002/2211-5463.12647.
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Catalytically inactive carbonic anhydrase-related proteins enhance transport of lactate by MCT1.
Aspatwar A
,
Tolvanen MEE
,
Schneider HP
,
Becker HM
,
Narkilahti S
,
Parkkila S
,
Deitmer JW
.
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Carbonic anhydrases (CA) catalyze the reversible hydration of CO2 to protons and bicarbonate and thereby play a fundamental role in the epithelial acid/base transport mechanisms serving fluid secretion and absorption for whole-body acid/base regulation. The three carbonic anhydrase-related proteins (CARPs) VIII, X, and XI, however, are catalytically inactive. Previous work has shown that some CA isoforms noncatalytically enhance lactate transport through various monocarboxylate transporters (MCT). Therefore, we examined whether the catalytically inactive CARPs play a role in lactate transport. Here, we report that CARP VIII, X, and XI enhance transport activity of the MCT MCT1 when coexpressed in Xenopus oocytes, as evidenced by the rate of rise in intracellular H+ concentration detected using ion-sensitive microelectrodes. Based on previous studies, we suggest that CARPs may function as a 'proton antenna' for MCT1, to drive proton-coupled lactate transport across the cell membrane.
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31033227
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Suomen Akatemia, Sigrid Juséliuksen Säätiö, Suomen Kulttuurirahasto, Jane ja Aatos Erkon Säätiö, Tekes, BE 4310/6-1 Deutsche Forschungsgemeinschaft, DE 231/24-2 Deutsche Forschungsgemeinschaft
Figure 1. Catalytically inactive CARP VIII, X, and XI facilitate MCT1 transport activity. (A) Original recordings of intracellular H+ concentration in oocytes expressing MCT1 (black trace), or coexpressing MCT1Â +Â CA8 (green trace), MCT1Â +Â CA10 (red trace), and MCT1Â +Â CA11 (blue trace), respectively, during application of 3 and 10Â mm lactate. (B) Rate of changes in intracellular H+ concentration (Î[H+]i/Ît) as induced by application of 3 and 10Â mm lactate, respectively, in oocytes expressing MCT1 (black), or coexpressing MCT1Â +Â CA8 (green), MCT1Â +Â CA10 (red), and MCT1Â +Â CA11 (blue). Leftâhand bars in each pair correspond to 3Â mm lactate and rightâhand bars to 10Â mm lactate, as indicated in the green bars. (C) Original recordings of intracellular H+ concentration in oocytes expressing MCT1 (black trace), or coexpressing MCT1Â +Â CA8 (green trace), MCT1Â +Â CA10 (red trace), and MCT1Â +Â CA11 (blue trace), respectively, during application of 5% CO2/10Â mm
HCO3-. (D) Rate of changes in intracellular H+ concentration (Î[H+]i/Ît) as induced by application of 5% CO2/10Â mm
HCO3-, respectively, in oocytes expressing MCT1 (black), or coexpressing MCT1 + CA8 (green), MCT1 + CA10 (red), and MCT1 + CA11 (blue). The numbers above the bars refer to number of experiments n. All values are depicted as mean + SEM. *Significance level of P â¤Â 0.05, **significance level of P â¤Â 0.01; n.s., no significance (Student's tâtest, as compared to oocytes with MCT1 expressed alone). (E) Original recording of intracellular H+ concentration in a H2Oâinjected control oocyte during application of 3 and 10 mm lactate and 5% CO2/10 mm
HCO3-.
Figure 2. Presence of CARP genes in injected Xenopus oocytes measured by RTâqPCR. Labels under the columns indicate the injected genes, native meaning not injected with any human gene. Measured transcripts of A, CA8; B, CA10; C, CA11; and D, SLC16A1 (MCT1). The bar graphs are the average values of three replicates (n = 10 in each group), and the error bars indicate standard deviation (SD).
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