PMID- 15218065
OWN - NLM
STAT- MEDLINE
DCOM- 20050127
LR  - 20181113
IS  - 0022-3751 (Print)
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Linking)
VI  - 559
IP  - Pt 1
DP  - 2004 Aug 15
TI  - Molecular mechanism of kNBC1-carbonic anhydrase II interaction in proximal tubule 
      cells.
PG  - 55-65
AB  - We have recently shown that carbonic anhydrase II (CAII) binds in vitro to the 
      C-terminus of the electrogenic sodium bicarbonate cotransporter kNBC1 (kNBC1-ct). 
      In the present study we determined the molecular mechanisms for the interaction 
      between the two proteins and whether kNBC1 and CAII form a transport metabolon in 
      vivo wherein bicarbonate is transferred from CAII directly to the cotransporter. 
      Various residues in the C-terminus of kNBC1 were mutated and the effect of these 
      mutations on both the magnitude of CAII binding and the function of kNBC1 
      expressed in mPCT cells was determined. Two clusters of acidic amino acids, 
      L(958)DDV and D(986)NDD in the wild-type kNBC1-ct involved in CAII binding were 
      identified. In both acidic clusters, the first aspartate residue played a more 
      important role in CAII binding than others. A significant correlation between the 
      magnitude of CAII binding and kNBC1-mediated flux was shown. The results 
      indicated that CAII activity enhances flux through the cotransporter when the 
      enzyme is bound to kNBC1. These data are the first direct evidence that a complex 
      of an electrogenic sodium bicarbonate cotransporter with CAII functions as a 
      transport metabolon.
FAU - Pushkin, Alexander
AU  - Pushkin A
AD  - Division of Nephrology, David Geffen School of Medicine at UCLA, Los Angeles, CA 
      90095, USA. apushkin@mednet.ucla.edu
FAU - Abuladze, Natalia
AU  - Abuladze N
FAU - Gross, Eitan
AU  - Gross E
FAU - Newman, Debra
AU  - Newman D
FAU - Tatishchev, Sergei
AU  - Tatishchev S
FAU - Lee, Ivan
AU  - Lee I
FAU - Fedotoff, Olga
AU  - Fedotoff O
FAU - Bondar, Galyna
AU  - Bondar G
FAU - Azimov, Rustam
AU  - Azimov R
FAU - Ngyuen, Matt
AU  - Ngyuen M
FAU - Kurtz, Ira
AU  - Kurtz I
LA  - eng
GR  - DK07789/DK/NIDDK NIH HHS/United States
GR  - R01 DK058563/DK/NIDDK NIH HHS/United States
GR  - T32 DK007789/DK/NIDDK NIH HHS/United States
GR  - DK63125/DK/NIDDK NIH HHS/United States
GR  - R01 DK063125/DK/NIDDK NIH HHS/United States
GR  - DK58563/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040624
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (SLC4A4 protein, human)
RN  - 0 (Slc4a4 protein, mouse)
RN  - 0 (Sodium-Bicarbonate Symporters)
RN  - EC 4.2.1.- (Carbonic Anhydrase II)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Carbonic Anhydrase II/genetics/*metabolism/physiology
MH  - Cells, Cultured
MH  - Humans
MH  - Kidney Tubules, Proximal/cytology/enzymology/*metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - Protein Binding/genetics
MH  - Sodium-Bicarbonate Symporters/genetics/*metabolism/physiology
PMC - PMC1665076
EDAT- 2004/06/26 05:00
MHDA- 2005/01/28 09:00
PMCR- 2005/08/15
CRDT- 2004/06/26 05:00
PHST- 2004/06/26 05:00 [pubmed]
PHST- 2005/01/28 09:00 [medline]
PHST- 2004/06/26 05:00 [entrez]
PHST- 2005/08/15 00:00 [pmc-release]
AID - jphysiol.2004.065110 [pii]
AID - 10.1113/jphysiol.2004.065110 [doi]
PST - ppublish
SO  - J Physiol. 2004 Aug 15;559(Pt 1):55-65. doi: 10.1113/jphysiol.2004.065110. Epub 
      2004 Jun 24.