PMID- 11606574
OWN - NLM
STAT- MEDLINE
DCOM- 20020131
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 51
DP  - 2001 Dec 21
TI  - A transport metabolon. Functional interaction of carbonic anhydrase II and 
      chloride/bicarbonate exchangers.
PG  - 47886-94
AB  - The cytoplasmic carboxyl-terminal domain of AE1, the plasma membrane 
      chloride/bicarbonate exchanger of erythrocytes, contains a binding site for 
      carbonic anhydrase II (CAII). To examine the physiological role of the AE1/CAII 
      interaction, anion exchange activity of transfected HEK293 cells was monitored by 
      following the changes in intracellular pH associated with AE1-mediated 
      bicarbonate transport. AE1-mediated chloride/bicarbonate exchange was reduced 
      50-60% by inhibition of endogenous carbonic anhydrase with acetazolamide, which 
      indicates that CAII activity is required for full anion transport activity. AE1 
      mutants, unable to bind CAII, had significantly lower transport activity than 
      wild-type AE1 (10% of wild-type activity), suggesting that a direct interaction 
      was required. To determine the effect of displacement of endogenous wild-type 
      CAII from its binding site on AE1, AE1-transfected HEK293 cells were 
      co-transfected with cDNA for a functionally inactive CAII mutant, V143Y. AE1 
      activity was maximally inhibited 61 +/- 4% in the presence of V143Y CAII. A 
      similar effect of V143Y CAII was found for AE2 and AE3cardiac anion exchanger 
      isoforms. We conclude that the binding of CAII to the AE1 carboxyl-terminus 
      potentiates anion transport activity and allows for maximal transport. The 
      interaction of CAII with AE1 forms a transport metabolon, a membrane protein 
      complex involved in regulation of bicarbonate metabolism and transport.
FAU - Sterling, D
AU  - Sterling D
AD  - Membrane Transport Group and Canadian Institutes of Health Research Group in 
      Molecular Biology of Membrane Proteins, Department of Physiology, University of 
      Alberta, Edmonton, Alberta T6G 2H7, Canada.
FAU - Reithmeier, R A
AU  - Reithmeier RA
FAU - Casey, J R
AU  - Casey JR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20011017
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Chloride-Bicarbonate Antiporters)
RN  - EC 4.2.1.- (Carbonic Anhydrase II)
SB  - IM
MH  - Amino Acid Sequence
MH  - Carbonic Anhydrase II/antagonists & inhibitors/*metabolism
MH  - Cell Line
MH  - Chloride-Bicarbonate Antiporters/*metabolism
MH  - Erythrocyte Membrane/metabolism
MH  - Humans
MH  - Molecular Sequence Data
MH  - Protein Binding
EDAT- 2001/10/19 10:00
MHDA- 2002/02/01 10:01
CRDT- 2001/10/19 10:00
PHST- 2001/10/19 10:00 [pubmed]
PHST- 2002/02/01 10:01 [medline]
PHST- 2001/10/19 10:00 [entrez]
AID - S0021-9258(19)40296-2 [pii]
AID - 10.1074/jbc.M105959200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 Dec 21;276(51):47886-94. doi: 10.1074/jbc.M105959200. Epub 2001 
      Oct 17.