Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
FEBS Open Bio
2019 Jul 01;97:1204-1211. doi: 10.1002/2211-5463.12647.
Show Gene links
Show Anatomy links
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
.
???displayArticle.abstract???
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.
???displayArticle.pubmedLink???
31033227
???displayArticle.pmcLink???PMC6609565 ???displayArticle.link???FEBS Open Bio ???displayArticle.grants???[+]
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 MCT1 + CA8 (green trace), MCT1 + CA10 (red trace), and MCT1 + CA11 (blue trace), respectively, during application of 3 and 10 mm lactate. (B) Rate of changes in intracellular H+ concentration (Δ[H+]i/Δt) as induced by application of 3 and 10 mm lactate, respectively, in oocytes expressing MCT1 (black), or coexpressing MCT1 + CA8 (green), MCT1 + CA10 (red), and MCT1 + CA11 (blue). Left‐hand bars in each pair correspond to 3 mm lactate and right‐hand bars to 10 mm lactate, as indicated in the green bars. (C) Original recordings of intracellular H+ concentration in oocytes expressing MCT1 (black trace), or coexpressing MCT1 + CA8 (green trace), MCT1 + CA10 (red trace), and MCT1 + CA11 (blue trace), respectively, during application of 5% CO2/10 mm
HCO3-. (D) Rate of changes in intracellular H+ concentration (Δ[H+]i/Δt) as induced by application of 5% CO2/10 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 ≤ 0.05, **significance level of P ≤ 0.01; n.s., no significance (Student's t‐test, as compared to oocytes with MCT1 expressed alone). (E) Original recording of intracellular H+ concentration in a H2O‐injected 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 RT–qPCR. 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).
Ames,
The proteoglycan-like domain of carbonic anhydrase IX mediates non-catalytic facilitation of lactate transport in cancer cells.
2018, Pubmed,
Xenbase
Ames,
The proteoglycan-like domain of carbonic anhydrase IX mediates non-catalytic facilitation of lactate transport in cancer cells.
2018,
Pubmed
,
Xenbase
Aspatwar,
Phylogeny and expression of carbonic anhydrase-related proteins.
2010,
Pubmed
Aspatwar,
Inactivation of ca10a and ca10b Genes Leads to Abnormal Embryonic Development and Alters Movement Pattern in Zebrafish.
2015,
Pubmed
Aspatwar,
Abnormal cerebellar development and ataxia in CARP VIII morphant zebrafish.
2013,
Pubmed
Aspatwar,
Carbonic anhydrase related proteins: molecular biology and evolution.
2014,
Pubmed
Becker,
Nonenzymatic proton handling by carbonic anhydrase II during H+-lactate cotransport via monocarboxylate transporter 1.
2008,
Pubmed
,
Xenbase
Becker,
Nonenzymatic augmentation of lactate transport via monocarboxylate transporter isoform 4 by carbonic anhydrase II.
2010,
Pubmed
,
Xenbase
Becker,
Carbonic anhydrase II increases the activity of the human electrogenic Na+/HCO3- cotransporter.
2007,
Pubmed
,
Xenbase
Becker,
Intramolecular proton shuttle supports not only catalytic but also noncatalytic function of carbonic anhydrase II.
2011,
Pubmed
,
Xenbase
Becker,
Transport activity of MCT1 expressed in Xenopus oocytes is increased by interaction with carbonic anhydrase.
2005,
Pubmed
,
Xenbase
Bergersen,
Is lactate food for neurons? Comparison of monocarboxylate transporter subtypes in brain and muscle.
2007,
Pubmed
Bouzier-Sore,
Competition between glucose and lactate as oxidative energy substrates in both neurons and astrocytes: a comparative NMR study.
2006,
Pubmed
Brooks,
The Science and Translation of Lactate Shuttle Theory.
2018,
Pubmed
Bröer,
Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH.
1998,
Pubmed
,
Xenbase
Cater,
Neuroprotective role of monocarboxylate transport during glucose deprivation in slice cultures of rat hippocampus.
2001,
Pubmed
DOLL,
[ON METABOLISM OF THE HUMAN HEART. II. OXYGEN AND CARBON DIOXIDE PRESSURE, PH, STANDARD BICARBONATE AND BASE EXCESS IN CORONARY VENOUS BLOOD DURING REST, DURING AND AFTER PHYSICAL WORK].
1965,
Pubmed
Deitmer,
The role of membrane acid/base transporters and carbonic anhydrases for cellular pH and metabolic processes.
2014,
Pubmed
Deitmer,
Electrogenic sodium-dependent bicarbonate secretion by glial cells of the leech central nervous system.
1991,
Pubmed
Fisher,
Atomic crystal and molecular dynamics simulation structures of human carbonic anhydrase II: insights into the proton transfer mechanism.
2007,
Pubmed
Forero-Quintero,
Membrane-anchored carbonic anhydrase IV interacts with monocarboxylate transporters via their chaperones CD147 and GP70.
2019,
Pubmed
,
Xenbase
Gertz,
Myocardial lactate metabolism: evidence of lactate release during net chemical extraction in man.
1981,
Pubmed
Halestrap,
The SLC16 gene family - structure, role and regulation in health and disease.
2013,
Pubmed
,
Xenbase
Hirota,
Carbonic anhydrase-related protein is a novel binding protein for inositol 1,4,5-trisphosphate receptor type 1.
2003,
Pubmed
Jamali,
Hypoxia-induced carbonic anhydrase IX facilitates lactate flux in human breast cancer cells by non-catalytic function.
2015,
Pubmed
,
Xenbase
Jiao,
Carbonic anhydrase-related protein VIII deficiency is associated with a distinctive lifelong gait disorder in waddles mice.
2005,
Pubmed
KEUL,
[ON METABOLISM OF THE HUMAN HEART. I. SUBSTRATE SUPPLY OF THE HEALTHY HUMAN HEART DURING REST, DURING AND AFTER PHYSICAL WORK].
1965,
Pubmed
Kaya,
Phenotypical spectrum of cerebellar ataxia associated with a novel mutation in the CA8 gene, encoding carbonic anhydrase (CA) VIII.
2011,
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
Klier,
Intracellular and extracellular carbonic anhydrases cooperate non-enzymatically to enhance activity of monocarboxylate transporters.
2014,
Pubmed
,
Xenbase
Kline,
Lactate improves cardiac efficiency after hemorrhagic shock.
2000,
Pubmed
Larkin,
Clustal W and Clustal X version 2.0.
2007,
Pubmed
Levy,
Myocardial lactate deprivation is associated with decreased cardiovascular performance, decreased myocardial energetics, and early death in endotoxic shock.
2007,
Pubmed
Martínez,
General requirement for harvesting antennae at ca and h channels and transporters.
2010,
Pubmed
McKenna,
Overview of the carbonic anhydrase family.
2014,
Pubmed
Nishimori,
Restoring catalytic activity to the human carbonic anhydrase (CA) related proteins VIII, X and XI affords isoforms with high catalytic efficiency and susceptibility to anion inhibition.
2013,
Pubmed
Noor,
Integration of a 'proton antenna' facilitates transport activity of the monocarboxylate transporter MCT4.
2017,
Pubmed
,
Xenbase
Noor,
A surface proton antenna in carbonic anhydrase II supports lactate transport in cancer cells.
2018,
Pubmed
,
Xenbase
Noor,
Analysis of the binding moiety mediating the interaction between monocarboxylate transporters and carbonic anhydrase II.
2015,
Pubmed
,
Xenbase
Pellerin,
Evidence supporting the existence of an activity-dependent astrocyte-neuron lactate shuttle.
1998,
Pubmed
Pfaffl,
A new mathematical model for relative quantification in real-time RT-PCR.
2001,
Pubmed
Schurr,
Lactate-supported synaptic function in the rat hippocampal slice preparation.
1988,
Pubmed
Sterky,
Carbonic anhydrase-related protein CA10 is an evolutionarily conserved pan-neurexin ligand.
2017,
Pubmed
Stridh,
Lactate flux in astrocytes is enhanced by a non-catalytic action of carbonic anhydrase II.
2012,
Pubmed
,
Xenbase
Taniuchi,
Developmental expression of carbonic anhydrase-related proteins VIII, X, and XI in the human brain.
2002,
Pubmed
Türkmen,
CA8 mutations cause a novel syndrome characterized by ataxia and mild mental retardation with predisposition to quadrupedal gait.
2009,
Pubmed
