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.

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.

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.

Inorganic carbon transport in some marine microalgal species

1991 ◽  
Vol 69 (5) ◽  
pp. 1032-1039 ◽  
Author(s):  
M. J. Merrett
Keyword(s):  
Carbonic Anhydrase ◽  
Inorganic Carbon ◽  
Silicone Oil ◽  
Ph Regulation ◽  
Carbonic Anhydrase Activity ◽  
Carbon Accumulation ◽  
Bicarbonate Transport ◽  
High Affinity ◽  
Inorganic Carbon Transport ◽  
Carbon Transport

Inorganic carbon transport was investigated in a range of marine microalgae. A small-celled strain of Stichococcus bacillaris, containing appreciable carbonic anhydrase activity, showed a high affinity for CO2, while measurement of the internal inorganic carbon pool by the silicone oil layer centrifugal filtering technique showed cells concentrated inorganic carbon up to 20-fold in relation to the external medium at pH 5.0 but not pH 8.3. The addition of 14CO2 or H14CO3− to cells in short-term kinetic experiments at pH 8.3 confirmed that only CO2 provides the exogenous substrate for substantial inorganic carbon accumulation within the cell. High-affinity HCO3− transport in Phaeodactylum tricornutum and Porphyridium purpureum is dependent on sodium ions, while intracellular carbonic anhydrase increased the steady-state flux of CO2 from inside the plasmalemma to Rubisco. In the presence of HCO3− the intracellular pH in cells of P. purpureum is 7.1 but on carbon starvation the pH falls to 6.0. Ethoxyzolamide blocks bicarbonate-dependent alkalinization of the cytosol, confirming a central role for carbonic anhydrase–bicarbonate in cytosolic pH regulation. Carbonic anhydrase activity is pH dependent in P. purpureum so synergistic interaction between CO2 uptake and bicarbonate transport may occur.

Anion exchange and anion-cation co-transport systems in mammalian cells

1982 ◽  
Vol 299 (1097) ◽  
pp. 519-535 ◽  
Keyword(s):  
Anion Exchange ◽  
Transport System ◽  
Mammalian Cells ◽  
Ph Regulation ◽  
Transport Systems ◽  
Regulatory Function ◽  
Ehrlich Cells ◽  
Ehrlich Ascites ◽  
Ehrlich Ascites Tumour ◽  
Anion Transfer

Electroneutral anion transfer in the Ehrlich ascites tumour cell has been found to occur by two separate mechanisms. One is an exchange diffusion system with many similarities to that found in erythrocytes, e.g. saturation kinetics with ‘self-inhibition’, a relatively pronounced temperature dependence, competitive interactions of Br- , NO - 3 and SCN- , and a low conductive P Cl - of 4 x 10 -8 cm s -1 . The main differences are that the Cl- flux in Ehrlich cells at 38 °C is one thousandth of the flux in red cells, and that the specificity of the system is less pronounced. It is suggested that the density of anion exchange sites in Ehrlich cells could be the same as in red blood cells, but with a lower turnover rate. The other system is an anion-cation co-transport system capable of mediating a secondary active Cl- influx. This system has a volume-regulatory function and is activated by a reduction in cell volume and intracellular [Cl-]. The two transport systems can be separated by using DIDS as an inhibitor of anion exchange and bumetanide as an inhibitor of co-transport. Under normal steady-state conditions Cl- flux is dominated by the exchange system. It is suggested that intracellular pH regulation can be achieved by the two systems operating in parallel, because the chloride disequilibrium maintained by the co-transport system can drive an influx of bicarbonate through the exchange mechanism.

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.

Functional characterization of NBC4: a new electrogenic sodium-bicarbonate cotransporter

2002 ◽  
Vol 282 (2) ◽  
pp. C408-C416 ◽  
Author(s):  
Pejvak Sassani ◽  
Alexander Pushkin ◽  
Eitan Gross ◽  
Alla Gomer ◽  
Natalia Abuladze ◽  
...  
Keyword(s):  
Sodium Bicarbonate ◽  
Mammalian Cells ◽  
Functional Characterization ◽  
Amino Acid Level ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Bicarbonate Transporter ◽  
Sodium Bicarbonate Cotransporter ◽  
Protein Variants

Sodium-bicarbonate cotransporters are homologous membrane proteins mediating the electrogenic or electroneutral transport of sodium and bicarbonate. Of the functionally characterized sodium-bicarbonate cotransporters (NBC), NBC1proteins are known to be electrogenic. Here we report the cloning and functional characterization of NBC4c, a new splice variant of the NBC4 gene. At the amino acid level, NBC4c is 56% identical to NBC1 protein variants and 40% identical to electroneutral NBC3. When expressed in mammalian cells, NBC4c mediates electrogenic sodium-bicarbonate cotransport. The transport of sodium and bicarbonate is chloride independent and is completely inhibited by DIDS. NBC4c transcripts were detected in several tissues including brain, heart, kidney, testis, pancreas, muscle, and peripheral blood leukocytes. The data indicate that NBC4c is an electrogenic sodium-bicarbonate cotransporter. The finding that both NBC1 and NBC4c proteins function as electrogenic sodium-bicarbonate cotransporters will aid in determining the structural motifs responsible for this unique functional property, which distinguishes these transporters from other members of the bicarbonate transporter superfamily.

scholarly journals Anion Transport in Heart

2000 ◽  
Vol 80 (1) ◽  
pp. 31-81 ◽  
Author(s):  
Joseph R. Hume ◽  
Dayue Duan ◽  
Mei Lin Collier ◽  
Jun Yamazaki ◽  
Burton Horowitz
Keyword(s):  
Protein Kinase ◽  
Anion Exchange ◽  
Mammalian Cells ◽  
Anion Transport ◽  
Transport Proteins ◽  
Cardiac Cells ◽  
Transport Processes ◽  
Anion Channels ◽  
Voltage Dependent Anion Channel ◽  
Intracellular Membranes

Anion transport proteins in mammalian cells participate in a wide variety of cell and intracellular organelle functions, including regulation of electrical activity, pH, volume, and the transport of osmolites and metabolites, and may even play a role in the control of immunological responses, cell migration, cell proliferation, and differentiation. Although significant progress over the past decade has been achieved in understanding electrogenic and electroneutral anion transport proteins in sarcolemmal and intracellular membranes, information on the molecular nature and physiological significance of many of these proteins, especially in the heart, is incomplete. Functional and molecular studies presently suggest that four primary types of sarcolemmal anion channels are expressed in cardiac cells: channels regulated by protein kinase A (PKA), protein kinase C, and purinergic receptors ( I Cl.PKA); channels regulated by changes in cell volume ( I Cl.vol); channels activated by intracellular Ca2+ ( I Cl.Ca); and inwardly rectifying anion channels ( I Cl.ir). In most animal species, I Cl.PKA is due to expression of a cardiac isoform of the epithelial cystic fibrosis transmembrane conductance regulator Cl− channel. New molecular candidates responsible for I Cl.vol, I Cl.Ca, and I Cl.ir(ClC-3, CLCA1, and ClC-2, respectively) have recently been identified and are presently being evaluated. Two isoforms of the band 3 anion exchange protein, originally characterized in erythrocytes, are responsible for Cl−/HCO3 − exchange, and at least two members of a large vertebrate family of electroneutral cotransporters (ENCC1 and ENCC3) are responsible for Na+-dependent Cl− cotransport in heart. A 223-amino acid protein in the outer mitochondrial membrane of most eukaryotic cells comprises a voltage-dependent anion channel. The molecular entities responsible for other types of electroneutral anion exchange or Cl− conductances in intracellular membranes of the sarcoplasmic reticulum or nucleus are unknown. Evidence of cardiac expression of up to five additional members of the ClC gene family suggest a rich new variety of molecular candidates that may underlie existing or novel Cl− channel subtypes in sarcolemmal and intracellular membranes. The application of modern molecular biological and genetic approaches to the study of anion transport proteins during the next decade holds exciting promise for eventually revealing the actual physiological, pathophysiological, and clinical significance of these unique transport processes in cardiac and other mammalian cells.

Characterization of two Mg2+transporters in sealed plasma membrane vesicles from rat liver

1998 ◽  
Vol 275 (4) ◽  
pp. C995-C1008 ◽  
Author(s):  
Christie Cefaratti ◽  
Andrea Romani ◽  
Antonio Scarpa
Keyword(s):  
Plasma Membrane ◽  
Rat Liver ◽  
Intracellular Signaling ◽  
Mammalian Cells ◽  
Plasma Membranes ◽  
Membrane Vesicles ◽  
Channel Blockers ◽  
Transport Mechanisms ◽  
Plasma Membrane Vesicles ◽  
New Information

The plasma membrane of mammalian cells possesses rapid Mg2+ transport mechanisms. The identity of Mg2+ transporters is unknown, and so are their properties. In this study, Mg2+ transporters were characterized using a biochemically and morphologically standardized preparation of sealed rat liver plasma membranes (LPM) whose intravesicular content could be set and controlled. The system has the advantages that it is not regulated by intracellular signaling machinery and that the intravesicular ion milieu can be designed. The results indicate that 1) LPM retain trapped intravesicular total Mg2+with negligible leak; 2) the addition of Na+ or Ca2+ induces a concentration- and temperature-dependent efflux corresponding to 30–50% of the intravesicular Mg2+; 3) the rate of flux is very rapid (137.6 and 86.8 nmol total Mg2+ ⋅ μm−2 ⋅ min−1after Na+ and Ca2+ addition, respectively); 4) coaddition of maximal concentrations of Na+ and Ca2+ induces an additive Mg2+ efflux; 5) both Na+- and Ca2+-stimulated Mg2+ effluxes are inhibited by amiloride, imipramine, or quinidine but not by vanadate or Ca2+ channel blockers; 6) extracellular Na+ or Ca2+ can stimulate Mg2+ efflux in the absence of Mg2+ gradients; and 7) Mg2+ uptake occurs in LPM loaded with Na+ but not with Ca2+, thus indicating that Na+/Mg2+but not Ca2+/Mg2+exchange is reversible. These data are consistent with the operation of two distinct Mg2+ transport mechanisms and provide new information on rates of Mg2+ transport, specificity of the cotransported ions, and reversibility of the transport.

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