PMID- 27860283
OWN - NLM
STAT- MEDLINE
DCOM- 20170622
LR  - 20220317
IS  - 1742-4658 (Electronic)
IS  - 1742-464X (Linking)
VI  - 284
IP  - 1
DP  - 2017 Jan
TI  - Integration of a 'proton antenna' facilitates transport activity of the 
      monocarboxylate transporter MCT4.
PG  - 149-162
LID - 10.1111/febs.13964 [doi]
AB  - Monocarboxylate transporters (MCTs) mediate the proton-coupled transport of 
      high-energy metabolites like lactate and pyruvate and are expressed in nearly 
      every mammalian tissue. We have shown previously that transport activity of MCT4 
      is enhanced by carbonic anhydrase II (CAII), which has been suggested to function 
      as a 'proton antenna' for the transporter. In the present study, we tested 
      whether creation of an endogenous proton antenna by introduction of a cluster of 
      histidine residues into the C-terminal tail of MCT4 (MCT4-6xHis) could facilitate 
      MCT4 transport activity when heterologously expressed in Xenopus oocytes. Our 
      results show that integration of six histidines into the C-terminal tail does 
      indeed increase transport activity of MCT4 to the same extent as did coexpression 
      of MCT4-WT with CAII. Transport activity of MCT4-6xHis could be further enhanced 
      by coexpression with extracellular CAIV, but not with intracellular CAII. 
      Injection of an antibody against the histidine cluster into MCT4-expressing 
      oocytes decreased transport activity of MCT4-6xHis, while leaving activity of 
      MCT4-WT unaltered. Taken together, these findings suggest that transport activity 
      of the proton-coupled monocarboxylate transporter MCT4 can be facilitated by 
      integration of an endogenous proton antenna into the transporter's C-terminal 
      tail.
CI  - (c) 2016 Federation of European Biochemical Societies.
FAU - Noor, Sina Ibne
AU  - Noor SI
AD  - Division of General Zoology, Department of Biology, University of Kaiserslautern, 
      Germany.
FAU - Pouyssegur, Jacques
AU  - Pouyssegur J
AD  - Centre Scientifique de Monaco (CSM), Monaco.
AD  - Institute for Research on Cancer & Aging (IRCAN), INSERM, Centre A. Lacassagne, 
      CNRS, University of Nice-Sophia Antipolis, France.
FAU - Deitmer, Joachim W
AU  - Deitmer JW
AD  - Division of General Zoology, Department of Biology, University of Kaiserslautern, 
      Germany.
FAU - Becker, Holger M
AU  - Becker HM
AD  - Division of General Zoology, Department of Biology, University of Kaiserslautern, 
      Germany.
LA  - eng
PT  - Journal Article
DEP - 20161207
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (His-His-His-His-His-His)
RN  - 0 (Monocarboxylic Acid Transporters)
RN  - 0 (Muscle Proteins)
RN  - 0 (Oligopeptides)
RN  - 0 (Protons)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Slc16a3 protein, rat)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 4QD397987E (Histidine)
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  - Antibodies, Neutralizing/pharmacology
MH  - Biological Transport/drug effects
MH  - Carbonic Anhydrase II/genetics/*metabolism
MH  - Carbonic Anhydrase IV/genetics/*metabolism
MH  - Gene Expression
MH  - Histidine/antagonists & inhibitors/genetics/*metabolism
MH  - Lactic Acid/metabolism
MH  - Microinjections
MH  - Monocarboxylic Acid Transporters/genetics/*metabolism
MH  - Muscle Proteins/genetics/*metabolism
MH  - Oligopeptides/antagonists & inhibitors/genetics/*metabolism
MH  - Oocytes/cytology/drug effects/metabolism
MH  - Protein Engineering
MH  - *Protons
MH  - Pyruvic Acid/metabolism
MH  - Rats
MH  - Recombinant Fusion Proteins/genetics/*metabolism
MH  - Xenopus laevis
OTO - NOTNLM
OT  - Xenopus oocytes
OT  - ion-selective microelectrodes
OT  - proton-collecting antenna
OT  - transport metabolon
EDAT- 2016/11/20 06:00
MHDA- 2017/06/24 06:00
CRDT- 2016/11/19 06:00
PHST- 2016/07/14 00:00 [received]
PHST- 2016/09/20 00:00 [revised]
PHST- 2016/11/11 00:00 [accepted]
PHST- 2016/11/20 06:00 [pubmed]
PHST- 2017/06/24 06:00 [medline]
PHST- 2016/11/19 06:00 [entrez]
AID - 10.1111/febs.13964 [doi]
PST - ppublish
SO  - FEBS J. 2017 Jan;284(1):149-162. doi: 10.1111/febs.13964. Epub 2016 Dec 7.