Interactions of transmembrane carbonic anhydrase, CAIX, with bicarbonate transporters

2007 ◽  
Vol 293 (2) ◽  
pp. C738-C748 ◽  
Author(s):  
Patricio E. Morgan ◽  
Silvia Pastoreková ◽  
Alan K. Stuart-Tilley ◽  
Seth L. Alper ◽  
Joseph R. Casey
Keyword(s):  
Gastric Mucosa ◽  
Carbonic Anhydrase ◽  
Catalytic Domain ◽  
Hek293 Cells ◽  
Bicarbonate Transport ◽  
Physical Interaction ◽  
Human Gastric Mucosa ◽  
Bicarbonate Transporter ◽  
Bicarbonate Transporters ◽  
Physical Interactions

Association of some plasma membrane bicarbonate transporters with carbonic anhydrase enzymes forms a bicarbonate transport metabolon to facilitate metabolic CO2-HCO3−conversions and coupled HCO3−transport. The transmembrane carbonic anhydrase, CAIX, with its extracellular catalytic site, is highly expressed in parietal and other cells of gastric mucosa, suggesting a role in acid secretion. We examined in transfected HEK293 cells the functional and physical interactions between CAIX and the parietal cell Cl−/HCO3−exchanger AE2 or the putative Cl−/HCO3−exchanger SLC26A7. Coexpression of CAIX increased AE2 transport activity by 28 ± 7% and also activated transport mediated by AE1 and AE3 (32 ± 10 and 37 ± 9%, respectively). In contrast, despite a transport rate comparable to that of AE3, coexpressed CAIX did not alter transport associated with SLC26A7. The CAIX-associated increase of AE2 activity did not result from altered AE2 expression or cell surface processing. CAIX was coimmunoprecipitated with the coexpressed SLC4 polypeptides AE1, AE2, and AE3, but not with SLC26A7. GST pull-down assays with a series of domain-deleted forms of CAIX revealed that the catalytic domain of CAIX mediated interaction with AE2. AE2 and CAIX colocalized in human gastric mucosa, as indicated by coimmunofluorescence. This is the first example of a functional and physical interaction between a bicarbonate transporter and a transmembrane carbonic anhydrase. We conclude that CAIX can bind to some Cl−/HCO3−exchangers to form a bicarbonate transport metabolon.

Bicarbonate transport proteins

2002 ◽  
Vol 80 (5) ◽  
pp. 483-497 ◽  
Author(s):  
Deborah Sterling ◽  
Joseph R Casey
Keyword(s):  
Carbonic Anhydrase ◽  
Sodium Bicarbonate ◽  
Anion Exchange ◽  
Mammalian Cells ◽  
Ph Regulation ◽  
Transport Proteins ◽  
Bicarbonate Transport ◽  
Transport Mechanisms ◽  
Bicarbonate Transporter ◽  
Bicarbonate Transporters

Bicarbonate is not freely permeable to membranes. Yet, bicarbonate must be moved across membranes, as part of CO2 metabolism and to regulate cell pH. Mammalian cells ubiquitously express bicarbonate transport proteins to facilitate the transmembrane bicarbonate flux. These bicarbonate transporters, which function by different transport mechanisms, together catalyse transmembrane bicarbonate movement. Recent advances have allowed the identification of several new bicarbonate transporter genes. Bicarbonate transporters cluster into two separate families: (i) the anion exachanger (AE) family of Cl–/HCO[Formula: see text] exchangers is related in sequence to the NBC family of Na+/HCO[Formula: see text] cotransporters and the Na+-dependent Cl–/HCO[Formula: see text] exchangers and (ii) some members of the SLC26a family of sulfate transporters will also transport bicarbonate but are not related in sequence to the AE/NBC family of transporters. This review summarizes our understanding of the mammalian bicarbonate transporter superfamily.Key words: bicarbonate transport, anion exchange, pH regulation, sodium/bicarbonate co-transport, chloride/bicarborate exchange, carbonic anhydrase.

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.

scholarly journals Mechanisms of acid–base regulation in seawater-acclimated green crabs (Carcinus maenas)

2016 ◽  
Vol 94 (2) ◽  
pp. 95-107 ◽  
Author(s):  
S. Fehsenfeld ◽  
D. Weihrauch
Keyword(s):  
Carbonic Anhydrase ◽  
Brackish Water ◽  
Carcinus Maenas ◽  
Ammonia Excretion ◽  
Respiratory Acidosis ◽  
Regulatory Mechanisms ◽  
Gill Epithelium ◽  
Acid Base ◽  
Bicarbonate Transporter ◽  
Bicarbonate Transporters

The present study investigated acid–base regulatory mechanisms in seawater-acclimated green crabs (Carcinus maenas (L., 1758)). In full-strength seawater, green crabs are osmoconformers so that the majority of the observed responses were attributed to ion fluxes based on acid–base compensatory responses alone. Similar to observations in brackish-water-acclimated C. maenas, seawater-acclimated green crabs exposed to hypercapnia rapidly accumulated HCO3− in their hemolymph, compensating for the respiratory acidosis caused by excess hemolymph pCO2. A full recovery from the decreased hemolymph pH after 48 h, however, was not observed. Gill perfusion experiments on anterior gill No. 5 indicated the involvement of all investigated genes (i.e., bicarbonate transporters, V-(H+)-ATPase, Na+/K+-ATPase, K+-channels, Na+/H+-exchanger, and carbonic anhydrase) in the excretion of acid–base equivalents. The most significant effects were observed when targeting a potentially cytoplasmic and (or) basolaterally localized V-(H+)-ATPase, as well as potentially basolaterally localized bicarbonate transporter (likely a Na+/HCO3−-cotransporter). In both cases, H+ accumulated in the hemolymph and CO2 excretion across the gill epithelium was significantly reduced or even reversed when blocking bicarbonate transporters. Based on the findings in this study, a working model for acid–base regulatory mechanisms and their link to ammonia excretion in the gill epithelium of C. maenas has been developed.

Effect of Bile Salts on Carbonic Anhydrase from Rat and Human Gastric Mucosa

1989 ◽  
Vol 24 (1) ◽  
pp. 28-32 ◽  
Author(s):  
M. Salomoni ◽  
E. Zuccato ◽  
P. Granelli ◽  
W. Montorsi ◽  
S. B. Doldi ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Carbonic Anhydrase ◽  
Bile Salts ◽  
Human Gastric Mucosa

Report on the Bicarbonate Transport Satellite Meeting at the 53rd Annual Meeting of the Canadian Society of Biochemistry, Molecular and Cellular Biology

2011 ◽  
Vol 89 (2) ◽  
pp. 83-84
Author(s):  
Reinhart A.F. Reithmeier ◽  
Joseph R. Casey
Keyword(s):  
Annual Meeting ◽  
Cellular Biology ◽  
Bicarbonate Transport ◽  
Canadian Society ◽  
Electron Crystallography ◽  
Bicarbonate Transporter ◽  
Bicarbonate Transporters ◽  
History Of ◽  
Health And Disease

The Bicarbonate Transport Meeting was held as a satellite meeting of the 53rd Annual Meeting of the Canadian Society of Biochemistry, Molecular and Cellular Biology (CSBMCB): Membrane Proteins in Health and Disease. The meeting covered the modern history of bicarbonate transporter proteins and brought together the major workers in the field. Ron Kopito recounted the story of the first determination of the amino acid sequence for a bicarbonate transporter, AE1/Band 3, 25 years earlier while working with Harvey Lodish at Harvard, while Tomohiro Yamaguchi and Teruhisa Hirai presented up-to-date data on AE1 structure obtained using electron crystallography. The meeting further spanned the spectrum of bicarbonate transporters, with sessions devoted to Cl–/HCO3– exchangers, Na+/HCO3– co-transporters, the link to carbonic anhydrase, and the SLC26 family of bicarbonate transporters expressed broadly in humans, yeast, and bacteria.

scholarly journals Carbonic Anhydrase IX Interacts with Bicarbonate Transporters in Lamellipodia and Increases Cell Migration via Its Catalytic Domain

2011 ◽  
Vol 287 (5) ◽  
pp. 3392-3402 ◽  
Author(s):  
Eliska Svastova ◽  
Wojciech Witarski ◽  
Lucia Csaderova ◽  
Ivan Kosik ◽  
Lucia Skvarkova ◽  
...  
Keyword(s):  
Cell Migration ◽  
Carbonic Anhydrase ◽  
Catalytic Domain ◽  
Carbonic Anhydrase Ix ◽  
Bicarbonate Transporters

H. pylori down-regulates TRAIL (DR4)-receptors in the human gastric mucosa, a possible mechanism for chronic persistence

2001 ◽  
Vol 120 (5) ◽  
pp. A81-A81
Author(s):  
B NEU ◽  
R RAD ◽  
M NEUHOFER ◽  
C TRAUTWEIN ◽  
M GERHARD ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Human Gastric Mucosa ◽  
H Pylori
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