PMID- 24338019
OWN - NLM
STAT- MEDLINE
DCOM- 20140410
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 289
IP  - 5
DP  - 2014 Jan 31
TI  - Intracellular and extracellular carbonic anhydrases cooperate non-enzymatically 
      to enhance activity of monocarboxylate transporters.
PG  - 2765-75
LID - 10.1074/jbc.M113.537043 [doi]
AB  - 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.
FAU - Klier, Michael
AU  - Klier M
AD  - From the Division of General Zoology, Department of Biology, University of 
      Kaiserslautern D-67653 Kaiserslautern, Germany and.
FAU - Andes, Fabian T
AU  - Andes FT
FAU - Deitmer, Joachim W
AU  - Deitmer JW
FAU - Becker, Holger M
AU  - Becker HM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131212
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Ketone Bodies)
RN  - 0 (Membrane Proteins)
RN  - 0 (Monocarboxylic Acid Transporters)
RN  - 0 (Muscle Proteins)
RN  - 0 (Oxygen Isotopes)
RN  - 0 (SLC16A4 protein, human)
RN  - 0 (Symporters)
RN  - 0 (monocarboxylate transport protein 1)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 8558G7RUTR (Pyruvic Acid)
RN  - EC 4.2.1.- (Carbonic Anhydrase II)
RN  - EC 4.2.1.- (Carbonic Anhydrase IV)
RN  - EC 4.2.1.1 (CA4 protein, human)
SB  - IM
MH  - Animals
MH  - Biological Transport/physiology
MH  - Carbonic Anhydrase II/metabolism
MH  - Carbonic Anhydrase IV/genetics/*metabolism
MH  - Cytosol/metabolism
MH  - Extracellular Space/metabolism
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Ketone Bodies/*metabolism
MH  - Lactic Acid/*metabolism
MH  - Membrane Proteins/metabolism
MH  - Monocarboxylic Acid Transporters/genetics/*metabolism
MH  - Muscle Proteins/genetics/*metabolism
MH  - Oocytes/physiology
MH  - Oxygen Isotopes/pharmacokinetics
MH  - Pyruvic Acid/*metabolism
MH  - Rats
MH  - Symporters/genetics/*metabolism
MH  - Xenopus
PMC - PMC3908409
OTO - NOTNLM
OT  - Ion-sensitive Electrodes
OT  - Lactic Acid
OT  - Protein Complexes
OT  - Protein Expression
OT  - Proton-collecting Antenna
OT  - Transport Metabolon
OT  - Xenopus Oocytes
OT  - pH Regulation
EDAT- 2013/12/18 06:00
MHDA- 2014/04/11 06:00
PMCR- 2015/01/31
CRDT- 2013/12/17 06:00
PHST- 2013/12/17 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2014/04/11 06:00 [medline]
PHST- 2015/01/31 00:00 [pmc-release]
AID - S0021-9258(19)74797-8 [pii]
AID - M113.537043 [pii]
AID - 10.1074/jbc.M113.537043 [doi]
PST - ppublish
SO  - J Biol Chem. 2014 Jan 31;289(5):2765-75. doi: 10.1074/jbc.M113.537043. Epub 2013 
      Dec 12.