PMID- 25561737
OWN - NLM
STAT- MEDLINE
DCOM- 20150508
LR  - 20210205
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 290
IP  - 7
DP  - 2015 Feb 13
TI  - Analysis of the binding moiety mediating the interaction between monocarboxylate 
      transporters and carbonic anhydrase II.
PG  - 4476-86
LID - 10.1074/jbc.M114.624577 [doi]
AB  - Proton-coupled monocarboxylate transporters (MCTs) mediate the exchange of high 
      energy metabolites like lactate between different cells and tissues. We have 
      reported previously that carbonic anhydrase II augments transport activity of 
      MCT1 and MCT4 by a noncatalytic mechanism, while leaving transport activity of 
      MCT2 unaltered. In the present study, we combined electrophysiological 
      measurements in Xenopus oocytes and pulldown experiments to analyze the direct 
      interaction between carbonic anhydrase II (CAII) and MCT1, MCT2, and MCT4, 
      respectively. Transport activity of MCT2-WT, which lacks a putative CAII-binding 
      site, is not augmented by CAII. However, introduction of a CAII-binding site into 
      the C terminus of MCT2 resulted in CAII-mediated facilitation of MCT2 transport 
      activity. Interestingly, introduction of three glutamic acid residues alone was 
      not sufficient to establish a direct interaction between MCT2 and CAII, but the 
      cluster had to be arranged in a fashion that allowed access to the binding moiety 
      in CAII. We further demonstrate that functional interaction between MCT4 and CAII 
      requires direct binding of the enzyme to the acidic cluster (431)EEE in the C 
      terminus of MCT4 in a similar fashion as previously shown for binding of CAII to 
      the cluster (489)EEE in the C terminus of MCT1. In CAII, binding to MCT1 and MCT4 
      is mediated by a histidine residue at position 64. Taken together, our results 
      suggest that facilitation of MCT transport activity by CAII requires direct 
      binding between histidine 64 in CAII and a cluster of glutamic acid residues in 
      the C terminus of the transporter that has to be positioned in surroundings that 
      allow access to CAII.
CI  - (c) 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Noor, Sina Ibne
AU  - Noor SI
AD  - From the Department of Biology, Division of Zoology/Membrane Transport and.
FAU - Dietz, Steffen
AU  - Dietz S
AD  - From the Department of Biology, Division of Zoology/Membrane Transport and.
FAU - Heidtmann, Hella
AU  - Heidtmann H
AD  - From the Department of Biology, Division of Zoology/Membrane Transport and the 
      Department of Biology, Division of General Zoology, University of Kaiserslautern, 
      D-67653 Kaiserslautern, Germany and.
FAU - Boone, Christopher D
AU  - Boone CD
AD  - the Department of Biochemistry and Molecular Biology, University of Florida, 
      Gainesville, Florida 32610.
FAU - McKenna, Robert
AU  - McKenna R
AD  - the Department of Biochemistry and Molecular Biology, University of Florida, 
      Gainesville, Florida 32610.
FAU - Deitmer, Joachim W
AU  - Deitmer JW
AD  - the Department of Biology, Division of General Zoology, University of 
      Kaiserslautern, D-67653 Kaiserslautern, Germany and.
FAU - Becker, Holger M
AU  - Becker HM
AD  - From the Department of Biology, Division of Zoology/Membrane Transport and 
      h.becker@biologie.uni-kl.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150105
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Monocarboxylic Acid Transporters)
RN  - 0 (Protein Isoforms)
RN  - EC 4.2.1.- (Carbonic Anhydrase II)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Biological Transport
MH  - Carbonic Anhydrase II/genetics/*metabolism
MH  - Electrophysiology
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Molecular Sequence Data
MH  - Monocarboxylic Acid Transporters/genetics/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Mutation/genetics
MH  - Oocytes/cytology/*metabolism
MH  - Protein Binding
MH  - Protein Isoforms
MH  - Rats
MH  - Sequence Homology, Amino Acid
MH  - Xenopus laevis/growth & development/metabolism
PMC - PMC4326851
OTO - NOTNLM
OT  - Ion-sensitive Electrode
OT  - Lactic Acid
OT  - Protein Complex
OT  - Protein Expression
OT  - Proton Transport
OT  - Xenopus
OT  - pH Regulation
EDAT- 2015/01/07 06:00
MHDA- 2015/05/09 06:00
PMCR- 2016/02/13
CRDT- 2015/01/07 06:00
PHST- 2015/01/07 06:00 [entrez]
PHST- 2015/01/07 06:00 [pubmed]
PHST- 2015/05/09 06:00 [medline]
PHST- 2016/02/13 00:00 [pmc-release]
AID - S0021-9258(19)47031-2 [pii]
AID - M114.624577 [pii]
AID - 10.1074/jbc.M114.624577 [doi]
PST - ppublish
SO  - J Biol Chem. 2015 Feb 13;290(7):4476-86. doi: 10.1074/jbc.M114.624577. Epub 2015 
      Jan 5.