scholarly journals Transport Activity of the High-affinity Monocarboxylate Transporter MCT2 Is Enhanced by Extracellular Carbonic Anhydrase IV but Not by Intracellular Carbonic Anhydrase II

2011 ◽  
Vol 286 (31) ◽  
pp. 27781-27791 ◽  
Author(s):  
Michael Klier ◽  
Christina Schüler ◽  
Andrew P. Halestrap ◽  
William S. Sly ◽  
Joachim W. Deitmer ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Monocarboxylate Transporter ◽  
Carbonic Anhydrase Ii ◽  
Transport Activity ◽  
High Affinity ◽  
Carbonic Anhydrase Iv

scholarly journals A surface proton antenna in carbonic anhydrase II supports lactate transport in cancer cells

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sina Ibne Noor ◽  
Somayeh Jamali ◽  
Samantha Ames ◽  
Silke Langer ◽  
Joachim W Deitmer ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Xenopus Oocytes ◽  
Proton Exchange ◽  
Monocarboxylate Transporter ◽  
Carbonic Anhydrase Ii ◽  
Transport Activity ◽  
Proton Shuttling ◽  
Mcf 7

Many tumor cells produce vast amounts of lactate and acid, which have to be removed from the cell to prevent intracellular lactacidosis and suffocation of metabolism. In the present study, we show that proton-driven lactate flux is enhanced by the intracellular carbonic anhydrase CAII, which is colocalized with the monocarboxylate transporter MCT1 in MCF-7 breast cancer cells. Co-expression of MCTs with various CAII mutants in Xenopus oocytes demonstrated that CAII facilitates MCT transport activity in a process involving CAII-Glu69 and CAII-Asp72, which could function as surface proton antennae for the enzyme. CAII-Glu69 and CAII-Asp72 seem to mediate proton transfer between enzyme and transporter, but CAII-His64, the central residue of the enzyme’s intramolecular proton shuttle, is not involved in proton shuttling between the two proteins. Instead, this residue mediates binding between MCT and CAII. Taken together, the results suggest that CAII features a moiety that exclusively mediates proton exchange with the MCT to facilitate transport activity.

The functional and physical relationship between the DRA bicarbonate transporter and carbonic anhydrase II

2002 ◽  
Vol 283 (5) ◽  
pp. C1522-C1529 ◽  
Author(s):  
Deborah Sterling ◽  
Nathan J. D. Brown ◽  
Claudiu T. Supuran ◽  
Joseph R. Casey
Keyword(s):  
Carbonic Anhydrase ◽  
Direct Interaction ◽  
Carbonic Anhydrase Ii ◽  
Bicarbonate Transport ◽  
Transport Activity ◽  
Physical Relationship ◽  
Hek 293 ◽  
Bicarbonate Transporter ◽  
293 Cells ◽  
Cytoplasmic Tails

COOH-terminal cytoplasmic tails of chloride/bicarbonate anion exchangers (AE) bind cytosolic carbonic anhydrase II (CAII) to form a bicarbonate transport metabolon, a membrane protein complex that accelerates transmembrane bicarbonate flux. To determine whether interaction with CAII affects the downregulated in adenoma (DRA) chloride/bicarbonate exchanger, anion exchange activity of DRA-transfected HEK-293 cells was monitored by following changes in intracellular pH associated with bicarbonate transport. DRA-mediated bicarbonate transport activity of 18 ± 1 mM H+ equivalents/min was inhibited 53 ± 2% by 100 mM of the CAII inhibitor, acetazolamide, but was unaffected by the membrane-impermeant carbonic anhydrase inhibitor, 1-[5-sulfamoyl-1,3,4-thiadiazol-2-yl-(aminosulfonyl-4-phenyl)]-2,6-dimethyl-4-phenyl-pyridinium perchlorate. Compared with AE1, the COOH-terminal tail of DRA interacted weakly with CAII. Overexpression of a functionally inactive CAII mutant, V143Y, reduced AE1 transport activity by 61 ± 4% without effect on DRA transport activity (105 ± 7% transport activity relative to DRA alone). We conclude that cytosolic CAII is required for full DRA-mediated bicarbonate transport. However, DRA differs from other bicarbonate transport proteins because its transport activity is not stimulated by direct interaction with CAII.

Regulation of the human NBC3 Na+/HCO3− cotransporter by carbonic anhydrase II and PKA

2004 ◽  
Vol 286 (6) ◽  
pp. C1423-C1433 ◽  
Author(s):  
Frederick B. Loiselle ◽  
Patricio E. Morgan ◽  
Bernardo V. Alvarez ◽  
Joseph R. Casey
Keyword(s):  
Carbonic Anhydrase ◽  
Recovery Rate ◽  
Dominant Negative ◽  
Carbonic Anhydrase Ii ◽  
Transport Activity ◽  
Wild Type ◽  
Hek 293 ◽  
Transfected Cells ◽  
293 Cells ◽  
Optimal Function

Human NBC3 is an electroneutral Na+/HCO3− cotransporter expressed in heart, skeletal muscle, and kidney in which it plays an important role in HCO3− metabolism. Cytosolic enzyme carbonic anhydrase II (CAII) catalyzes the reaction CO2 + H2O ⇆ HCO3− + H+ in many tissues. We investigated whether NBC3, like some Cl−/HCO3− exchange proteins, could bind CAII and whether PKA could regulate NBC3 activity through modulation of CAII binding. CAII bound the COOH-terminal domain of NBC3 (NBC3Ct) with Kd = 101 nM; the interaction was stronger at acid pH. Cotransfection of HEK-293 cells with NBC3 and CAII recruited CAII to the plasma membrane. Mutagenesis of consensus CAII binding sites revealed that the D1135-D1136 region of NBC3 is essential for CAII/NBC3 interaction and for optimal function, because the NBC3 D1135N/D1136N retained only 29 ± 22% of wild-type activity. Coexpression of the functionally dominant-negative CAII mutant V143Y with NBC3 or addition of 100 μM 8-bromoadenosine to NBC3 transfected cells reduced intracellular pH (pHi) recovery rate by 31 ± 3, or 38 ± 7%, respectively, relative to untreated NBC3 transfected cells. The effects were additive, together decreasing the pHi recovery rate by 69 ± 12%, suggesting that PKA reduces transport activity by a mechanism independently of CAII. Measurements of PKA-dependent phosphorylation by mass spectroscopy and labeling with [γ-32P]ATP showed that NBC3Ct was not a PKA substrate. These results demonstrate that NBC3 and CAII interact to maximize the HCO3− transport rate. Although PKA decreased NBC3 transport activity, it did so independently of the NBC3/CAII interaction and did not involve phosphorylation of NBC3Ct.

scholarly journals Intrinsic thermodynamics of high affinity inhibitor binding to recombinant human carbonic anhydrase IV

2017 ◽  
Vol 47 (3) ◽  
pp. 271-290 ◽  
Author(s):  
Aurelija Mickevičiūtė ◽  
David D. Timm ◽  
Marius Gedgaudas ◽  
Vaida Linkuvienė ◽  
Zhiwei Chen ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Inhibitor Binding ◽  
High Affinity ◽  
Human Carbonic Anhydrase ◽  
Carbonic Anhydrase Iv

scholarly journals Structures of murine carbonic anhydrase IV and human carbonic anhydrase II complexed with brinzolamide: Molecular basis of isozyme-drug discrimination

1998 ◽  
Vol 7 (3) ◽  
pp. 556-563 ◽  
Author(s):  
Travis Stams ◽  
Yun Chen ◽  
David W. Christianson ◽  
P. Ann Boriack-Sjodin ◽  
Jonathan D. Hurt ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Drug Discrimination ◽  
Molecular Basis ◽  
Carbonic Anhydrase Ii ◽  
Human Carbonic Anhydrase ◽  
Carbonic Anhydrase Iv

Expression of carbonic anhydrase IV in carbonic anhydrase II-deficient mice

1997 ◽  
Vol 273 (2) ◽  
pp. F234-F245 ◽  
Author(s):  
L. P. Brion ◽  
W. Cammer ◽  
L. M. Satlin ◽  
C. Suarez ◽  
B. J. Zavilowitz ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Carbonic Anhydrase ◽  
Western Blot ◽  
Renal Cortex ◽  
Specific Activity ◽  
Carbonic Anhydrase Ii ◽  
Chronic Metabolic Acidosis ◽  
Congenital Deficiency ◽  
Carbonic Anhydrase Iv ◽  
Deficient Mice

Chronic metabolic acidosis (CMA) in the rabbit upregulates carbonic anhydrase (CA) IV in the proximal convoluted tubule (PCT). This study was designed to assess CA IV expression in a model of CMA in the mouse, i.e., congenital deficiency in CA II [CA(II)D]. In female CA(II)D mice, CA IV specific activity but not CA IV immunoreactivity was upregulated in the renal cortex, specifically in microdissected PCTs. Western blot analysis showed higher expression of CA IV immunoreactive protein in renal membranes from males than in those from females.

scholarly journals Activity and distribution of intracellular carbonic anhydrase II and their effects on the transport activity of anion exchanger AE1/SLC4A1

2013 ◽  
Vol 591 (20) ◽  
pp. 4963-4982 ◽  
Author(s):  
Samer Al-Samir ◽  
Symeon Papadopoulos ◽  
Renate J. Scheibe ◽  
Joachim D. Meißner ◽  
Jean-Pierre Cartron ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Anion Exchanger ◽  
Carbonic Anhydrase Ii ◽  
Transport Activity
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