PMID- 21680735
OWN - NLM
STAT- MEDLINE
DCOM- 20111010
LR  - 20220317
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 286
IP  - 31
DP  - 2011 Aug 5
TI  - Transport activity of the high-affinity monocarboxylate transporter MCT2 is 
      enhanced by extracellular carbonic anhydrase IV but not by intracellular carbonic 
      anhydrase II.
PG  - 27781-91
LID - 10.1074/jbc.M111.255331 [doi]
AB  - The ubiquitous enzyme carbonic anhydrase isoform II (CAII) has been shown to 
      enhance transport activity of the proton-coupled monocarboxylate transporters 
      MCT1 and MCT4 in a non-catalytic manner. In this study, we investigated the role 
      of cytosolic CAII and of the extracellular, membrane-bound CA isoform IV (CAIV) 
      on the lactate transport activity of the high-affinity monocarboxylate 
      transporter MCT2, heterologously expressed in Xenopus oocytes. In contrast to 
      MCT1 and MCT4, transport activity of MCT2 was not altered by CAII. However, 
      coexpression of CAIV with MCT2 resulted in a significant increase in MCT2 
      transport activity when the transporter was coexpressed with its associated 
      ancillary protein GP70 (embigin). The CAIV-mediated augmentation of MCT2 activity 
      was independent of the catalytic activity of the enzyme, as application of the 
      CA-inhibitor ethoxyzolamide or coexpressing the catalytically inactive mutant 
      CAIV-V165Y did not suppress CAIV-mediated augmentation of MCT2 transport 
      activity. Furthermore, exchange of His-88, mediating an intramolecular 
      H(+)-shuttle in CAIV, to alanine resulted only in a slight decrease in 
      CAIV-mediated augmentation of MCT2 activity. The data suggest that extracellular 
      membrane-bound CAIV, but not cytosolic CAII, augments transport activity of MCT2 
      in a non-catalytic manner, possibly by facilitating a proton pathway other than 
      His-88.
FAU - Klier, Michael
AU  - Klier M
AD  - Abteilung fur Allgemeine Zoologie, Fachbereich Biologie, Technische Universitat 
      Kaiserslautern, P. O. Box 3049, 67653 Kaiserslautern, Germany.
FAU - Schuler, Christina
AU  - Schuler C
FAU - Halestrap, Andrew P
AU  - Halestrap AP
FAU - Sly, William S
AU  - Sly WS
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 - 20110616
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA Primers)
RN  - 0 (Monocarboxylic Acid Transporters)
RN  - 0 (SLC16A7 protein, human)
RN  - 6SO6U10H04 (Biotin)
RN  - EC 4.2.1.- (Carbonic Anhydrase II)
RN  - EC 4.2.1.- (Carbonic Anhydrase IV)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Biotin/metabolism
MH  - Carbonic Anhydrase II/*metabolism
MH  - Carbonic Anhydrase IV/*metabolism
MH  - DNA Primers
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Immunohistochemistry
MH  - Monocarboxylic Acid Transporters/*metabolism
MH  - Polymerase Chain Reaction
MH  - Protein Transport
MH  - Xenopus
PMC - PMC3149368
EDAT- 2011/06/18 06:00
MHDA- 2011/10/11 06:00
PMCR- 2012/08/05
CRDT- 2011/06/18 06:00
PHST- 2011/06/18 06:00 [entrez]
PHST- 2011/06/18 06:00 [pubmed]
PHST- 2011/10/11 06:00 [medline]
PHST- 2012/08/05 00:00 [pmc-release]
AID - S0021-9258(20)50380-3 [pii]
AID - M111.255331 [pii]
AID - 10.1074/jbc.M111.255331 [doi]
PST - ppublish
SO  - J Biol Chem. 2011 Aug 5;286(31):27781-91. doi: 10.1074/jbc.M111.255331. Epub 2011 
      Jun 16.