The Extracellular Component of a Transport Metabolon

Cytosolic carbonic anhydrase II (CAII) and the cytoplasmic C-terminal tails of chloride/bicarbonate anion exchange (AE) proteins associate to form a bicarbonate transport metabolon, which maximizes the bicarbonate transport rate. To determine whether cell surface-anchored carbonic anhydrase IV (CAIV) interacts with AE proteins to accelerate the bicarbonate transport rate, AE1-mediated bicarbonate transport was monitored in transfected HEK293 cells. Expression of the inactive CAII V143Y mutant blocked the interaction between endogenous cytosolic CAII and AE1, AE2, and AE3 and inhibited their transport activity (53 ± 3, 49 ± 10, and 35 ± 1% inhibition, respectively). However, in the presence of V143Y CAII, expression of CAIV restored full functional activity to AE1, AE2, and AE3 (AE1, 101 ± 3; AE2, 85 ± 5; AE3, 108 ± 1%). In Triton X-100 extracts of transfected HEK293 cells, resolved by sucrose gradient ultracentrifugation, CAIV recruitment to the position of AE1 suggested a physical interaction between CAIV and AE1. Gel overlay assays showed a specific interaction between CAIV and AE1, AE2, and AE3. Glutathione S-transferase pull-down assays revealed that the interaction between CAIV and AE1 occurs on the large fourth extracellular loop of AE1. We conclude that AE1 and CAIV interact on extracellular loop 4 of AE1, forming the extracellular component of a bicarbonate transport metabolon, which accelerates the rate of AE-mediated bicarbonate transport. Cytosolic carbonic anhydrase II (CAII) and the cytoplasmic C-terminal tails of chloride/bicarbonate anion exchange (AE) proteins associate to form a bicarbonate transport metabolon, which maximizes the bicarbonate transport rate. To determine whether cell surface-anchored carbonic anhydrase IV (CAIV) interacts with AE proteins to accelerate the bicarbonate transport rate, AE1-mediated bicarbonate transport was monitored in transfected HEK293 cells. Expression of the inactive CAII V143Y mutant blocked the interaction between endogenous cytosolic CAII and AE1, AE2, and AE3 and inhibited their transport activity (53 ± 3, 49 ± 10, and 35 ± 1% inhibition, respectively). However, in the presence of V143Y CAII, expression of CAIV restored full functional activity to AE1, AE2, and AE3 (AE1, 101 ± 3; AE2, 85 ± 5; AE3, 108 ± 1%). In Triton X-100 extracts of transfected HEK293 cells, resolved by sucrose gradient ultracentrifugation, CAIV recruitment to the position of AE1 suggested a physical interaction between CAIV and AE1. Gel overlay assays showed a specific interaction between CAIV and AE1, AE2, and AE3. Glutathione S-transferase pull-down assays revealed that the interaction between CAIV and AE1 occurs on the large fourth extracellular loop of AE1. We conclude that AE1 and CAIV interact on extracellular loop 4 of AE1, forming the extracellular component of a bicarbonate transport metabolon, which accelerates the rate of AE-mediated bicarbonate transport. carbonic anhydrase anion exchanger 2′,7′–bis(2-carboxyethyl)–5(6)-carboxyfluorescein-acetoxymethyl ester extracellular loop enhanced chemiluminescence glutathione S-transferase fusion of the third extracellular loop of AE1 to GST fusion of the fourth extracellular loop of AE1 to GST human embryonic kidney intracellular pH platelet-derived growth factor Carbonic anhydrases (CA)1 (EC 4.2.1.1) are a family of zinc metalloenzymes that catalyze the rapid hydration/dehydration of CO2/HCO3−. Bicarbonate transport proteins are closely associated functionally with CA and together they eliminate the metabolic waste, CO2, from the body. There are 14 mammalian isoforms of CA identified to date, varying in catalytic activity and tissue distribution (2Mori K. Ogawa Y. Ebihara K. Tamura N. Tashiro K. Kuwahara T. Mukoyama M. Sugawara A. Ozaki S. Tanaka I. Nakao K. J. Biol. Chem. 1999; 274: 15701-15705Abstract Full Text Full Text PDF PubMed Scopus (116) Google Scholar, 3Kivela A. Parkkila S. Saarnio J. Karttunen T.J. Kivela J. Parkkila A.K. Waheed A. Sly W.S. Grubb J.H. Shah G. Tureci O. Rajaniemi H. Am. J. Pathol. 2000; 156: 577-584Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar, 4Tureci O. Sahin U. Vollmar E. Siemer S. Gottert E. Seitz G. Parkkila A.K. Shah G.N. Grubb J.H. Pfreundschuh M. Sly W.S. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 7608-7613Crossref PubMed Scopus (323) Google Scholar). CAII, found predominantly in red blood cells, has been shown not only to bind to proteins of the AE family of Cl−/HCO3− anion exchange proteins but also to potentiate their transport activity by formation of a transport metabolon (5Vince J.W. Reithmeier R.A.F. J. Biol. Chem. 1998; 273: 28430-28437Abstract Full Text Full Text PDF PubMed Scopus (212) Google Scholar, 6Vince J.W. Reithmeier R.A.F. Biochemistry. 2000; 39: 5527-5533Crossref PubMed Scopus (162) Google Scholar, 7Vince J.W. Carlsson U. Reithmeier R.A.F. Biochemistry. 2000; 39: 13344-13349Crossref PubMed Scopus (98) Google Scholar, 8Sterling D. Reithmeier R.A. Casey J.R. J. Biol. Chem. 2001; 276: 47886-47894Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar). A metabolon is a complex of proteins involved in a metabolic pathway that allows metabolites to move rapidly from one active site to the next (9Srere P.A. Trends Biochem. Sci. 1985; 10: 109-110Abstract Full Text PDF Scopus (244) Google Scholar, 10Srere P.A. Annu. Rev. Biochem. 1987; 56: 89-124Crossref PubMed Scopus (811) Google Scholar). The physical association of CAII with AE localizes the site of substrate (HCO3−) production to the transport site, thus creating a transport metabolon. The CA·AE complex may also accelerate bicarbonate flux in part because of the increased CAII activity found upon interaction with its binding site on AE (11Scozzafava A. Supuran C.T. Bioorg. Med. Chem. Lett. 2002; 12: 1177-1180Crossref PubMed Scopus (62) Google Scholar). The AE family of proteins is comprised of AE1, AE2, and AE3 (12Grinstein S. Ship S. Rothstein A. Biochim. Biophys. Acta. 1979; 507: 294-304Crossref Scopus (184) Google Scholar, 13Kopito R.R. Lee B.S. Simmons D.M. Lindsey A.E. Morgans C.W. Schneider K. Cell. 1989; 59: 927-937Abstract Full Text PDF PubMed Scopus (207) Google Scholar, 14Kudrycki K.E. Newman P.R. Schull G.E. J. Biol. Chem. 1990; 265: 462-471Abstract Full Text PDF PubMed Google Scholar, 15Alper S.L. Kopito R.R. Libresco S.M. Lodish H.F. J. Biol. Chem. 1988; 263: 17092-17099Abstract Full Text PDF PubMed Google Scholar). The recently cloned AE4, although termed AE, shares little similarity with the other members of the AE family and is in fact more similar to the sodium/bicarbonate co-transporters (16Tsuganezawa H. Kobayashi K. Iyori M. Araki T. Koizumi A. Watanabe S. Kaneko A. Fukao T. Monkawa T. Yoshida T. Kim D.K. Kanai Y. Endou H. Hayashi M. Saruta T. J. Biol. Chem. 2001; 276: 8180-8189Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar). AE1 is expressed abundantly in erythrocytes and a truncated form is also present in the kidney and heart (17Kollert-Jons A. Wagner S. Hubner S. Appelhans H. Drenckhahn D. Am. J. Physiol. 1993; 265: F813-F821PubMed Google Scholar, 18Richards S.M. Jaconi M.E. Vassort G. Puceat M. J. Cell Sci. 1999; 112: 1519-1528Crossref PubMed Google Scholar). AE2 is almost ubiquitous, whereas AE3 expression is restricted to the brain, heart, and retina (13Kopito R.R. Lee B.S. Simmons D.M. Lindsey A.E. Morgans C.W. Schneider K. Cell. 1989; 59: 927-937Abstract Full Text PDF PubMed Scopus (207) Google Scholar, 15Alper S.L. Kopito R.R. Libresco S.M. Lodish H.F. J. Biol. Chem. 1988; 263: 17092-17099Abstract Full Text PDF PubMed Google Scholar, 19Linn S.C. Kudrycki K.E. Schull G.E. J. Biol. Chem. 1992; 267: 7927-7935Abstract Full Text PDF PubMed Google Scholar,20Kobayashi S. Morgans C.W. Casey J.R. Kopito R.R. J. Neurosci. 1994; 14: 6266-6279Crossref PubMed Google Scholar). Unlike cytosolic CAII, CAIV is anchored to the extracellular surface of the plasma by a thus in the extracellular A. Sly W.S. G. Biochem. Biophys. 1992; PubMed Scopus Google Scholar). and with functional CAIV expression to the heart, brain, and S. Sly W.S. G. J. 1998; PubMed Scopus Google Scholar, J. Biol. Chem. Full Text PDF PubMed Google Scholar, Am. J. Physiol. 1994; Google Scholar, W.S. T. 1985; PubMed Scopus Google Scholar, 1989; Full Text PDF PubMed Scopus Google Scholar, Biochim. Biophys. Acta. PubMed Scopus Google Scholar, M. J. Neurosci. 2000; PubMed Google Scholar, Waheed A. Sly W.S. Proc. Natl. Acad. Sci. U. S. A. 1992; PubMed Scopus Google Scholar, Waheed A. Sly W.S. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, C.W. I. Physiol. 1999; PubMed Scopus Google of which AE CAIV with a catalytic activity of which is with CAII Waheed A. T. Sly W.S. Biochemistry. PubMed Scopus Google Scholar). The CA isoforms in their to with CAIV to CAII Waheed A. T. Sly W.S. Biochemistry. PubMed Scopus Google Scholar). CAIV is in that that to its in a of that CAII T. S. Waheed A. Sly W.S. Proc. Natl. Acad. Sci. U. S. A. 1992; PubMed Scopus Google Scholar). The tissue distribution of AE proteins is by the expression of CA isoforms the body. only one CA other The extracellular CAIV is expressed in the heart, but is cytosolic CAII S. Sly W.S. G. J. 1998; PubMed Scopus Google Scholar, D. A. G. Biochem. J. 1992; PubMed Scopus Google Scholar). erythrocytes CAII, and CAIV (5Vince J.W. Reithmeier R.A.F. J. Biol. Chem. 1998; 273: 28430-28437Abstract Full Text Full Text PDF PubMed Scopus (212) Google Scholar, C.W. I. Physiol. 1999; PubMed Scopus Google Scholar). The which to of CAIV and cytosolic CAII Am. J. Physiol. 1994; Google Scholar, W.S. T. 1985; PubMed Scopus Google Scholar, 1989; Full Text PDF PubMed Scopus Google Scholar, Biochim. Biophys. Acta. PubMed Scopus Google Scholar). CAII localizes to the of of and is the of W.S. T. 1985; PubMed Scopus Google whereas CAIV localizes to the surface of and S. Am. J. Physiol. 2000; Scholar). CAIV a in bicarbonate by the kidney C.W. J. Biol. Chem. 1993; Full Text PDF PubMed Google the pH in the E. Biochim. Biophys. Acta. PubMed Scopus Google Scholar). CAIV is also found on the surface of J. Biol. Chem. Full Text PDF PubMed Google and in the of its presence may the CA that are in the of Waheed A. Sly W.S. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). of of carbonic anhydrases and bicarbonate The of bicarbonate and transport to the physical and functional between AE proteins and In found a functional interaction between AE proteins and Expression of CAIV on the bicarbonate transport rate in AE1 and cytosolic CAII, because CAII maximizes the bicarbonate flux was not to to CAII because CA extracellular CAIV and intracellular a form of CAII to the of cytosolic CAII on AE transport activity and the of CAIV in AE-mediated bicarbonate transport We found that CAII, CAIV also accelerates AE-mediated bicarbonate transport the of on sucrose overlay and GST pull-down assays conclude that is a physical association between extracellular CAIV and the transport AE1. The interaction occurs on the fourth extracellular loop of AE1. together CAIV and AE functionally and interact to form the extracellular component of a bicarbonate transport metabolon, which AE-mediated bicarbonate transport. to and and from was from from to was from expression the CAIV was a from S. Am. J. Physiol. 2000; and the V143Y CAII Biochemistry. PubMed Scopus Google Scholar). Expression AE and CA proteins been D. Reithmeier R.A. Casey J.R. J. Biol. Chem. 2001; 276: 47886-47894Abstract Full Text Full Text PDF PubMed Scopus (315) Google J.R. Y. Kopito R.R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, B.S. Kopito R.R. J. Biol. Chem. Full Text PDF PubMed Google Scholar, D. Casey J.R. Biochem. J. 1999; PubMed Scopus Google Scholar). was AE and CA proteins expressed by of HEK293 J. J. Scopus Google the S. Lindsey A.E. Kopito R.R. Physiol. 1993; Google Scholar). in in with and expression GST fusion proteins of the glutathione S-transferase to to the third fourth extracellular loop of AE1 AE1 a the and and site of the third The was with and the expression in the to the The and and in the to the fourth extracellular loop The and by with a and was The and a to of growth with was to of The was with the A was was and growth was to The was and in by and with Triton X-100 to a of 1% with the was to with and to with The was and the was with The fusion proteins with glutathione glutathione in pH HEK293 cells, in tissue transfected with a J.R. Y. Kopito R.R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google to expression of AE1 anion exchange also with D. Reithmeier R.A. Casey J.R. J. Biol. Chem. 2001; 276: 47886-47894Abstract Full Text Full Text PDF PubMed Scopus (315) Google to expression of human and mutant CAII, and also with a to CAIV S. Am. J. Physiol. 2000; Scholar). B.S. Kopito R.R. J. Biol. Chem. Full Text PDF PubMed Google and D. Casey J.R. Biochem. J. 1999; PubMed Scopus Google AE2 and AE3 with and of the tissue by of of 1% pH and to to and a was by resolved by on PubMed Scopus Google Scholar). to by in of and H. T. J. Proc. Natl. Acad. Sci. U. S. A. 1979; PubMed Scopus Google Scholar). blocked by in pH and in of of J. Kopito Casey J.R. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google of CAII of CAIV S. Am. J. Physiol. 2000; Scholar). with with of to with to and with to with and and a exchange activity was monitored a D. Casey J.R. Biochem. J. 1999; PubMed Scopus Google Scholar). HEK293 on in and in 4 of in a and with pH and with was monitored a of and and of the A. E. Biochemistry. 1979; PubMed Scopus Google pH between and to pH of of pH by of the and to of flux the plasma to the A. Physiol. Rev. PubMed Scopus Google D. Casey J.R. Biochem. J. 1999; PubMed Scopus Google Scholar). In the transport activity of transfected was from the rate to that only of the AE transport HEK293 transfected with AE1 CAIV with The to was a of the and Cell. 1992; Full Text PDF PubMed Scopus Google Scholar). on in of 1% Triton pH with the with in a and to sucrose by of of sucrose in Triton X-100 and on of sucrose in which sucrose also been in Triton in a 4 and A of was by of of of resolved by on and HEK293 in transfected with AE1, AE2, AE3, CAIV AE in and CAIV in of with and of of transfected with AE blocked with and in 1% of the cell from cells. in and CAIV GST fusion proteins of the third and fourth extracellular loop of AE1 in a GST pull-down of GST to of in of pH with Cell of by of of in of to the and 4 with and the was The was with and the by in resolved by on to a and CAIV are expressed ± of was a with functional proteins expressed in HEK293 cells. cell endogenous CAII D. Reithmeier R.A. Casey J.R. J. Biol. Chem. 2001; 276: 47886-47894Abstract Full Text Full Text PDF PubMed Scopus (315) Google of AE (13Kopito R.R. Lee B.S. Simmons D.M. Lindsey A.E. Morgans C.W. Schneider K. Cell. 1989; 59: 927-937Abstract Full Text PDF PubMed Scopus (207) Google Scholar). the B.S. Kopito R.R. J. Biol. Chem. Full Text PDF PubMed Google which the of the with AE1, the functionally inactive mutant V143Y CAII, and that of HEK293 with AE1, CAII, and CAIV in expression of transfected with showed with AE CAIV but the presence of endogenous CAII a in CAIV on The of is not but the in is with S. Am. J. Physiol. 2000; from on the To anion exchange transfected on and with a The in a and with and In the cell and bicarbonate in cell In the with the cell in exchange to cell the A. E. Biochemistry. 1979; PubMed Scopus Google in of of in intracellular pH associated with bicarbonate exchange To determine the of CAIV on AE transport activity HEK293 with AE1, AE2, AE3 and CAIV of AE proteins with CAIV on the AE-mediated bicarbonate transport activity not of CAIV may not been because HEK293 CAII to AE transport activity D. Reithmeier R.A. Casey J.R. J. Biol. Chem. 2001; 276: 47886-47894Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar). To CAIV on AE transport activity from that of CAII, a functionally inactive V143Y CAII mutant Biochemistry. PubMed Scopus Google Scholar). of HEK293 with V143Y CAII in expression endogenous CAII V143Y CAII in a to functional CAII from binding thus AE transport activity by of the functional metabolon D. Reithmeier R.A. Casey J.R. J. Biol. Chem. 2001; 276: 47886-47894Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar). that expression of V143Y CAII AE1 transport activity (53 ± of CAIV to AE1 and V143Y CAII the transport activity of AE1, the bicarbonate transport rate to the AE1 and CAII The of AE1 transport activity a functional interaction between AE1 and that the AE1 bicarbonate transport rate by interaction with CAII To determine whether the of AE1 transport activity by CAIV was on CAIV catalytic the transport activity of AE1, V143Y CAII, and CAIV and with the CA is a of CAII and CAIV that has on anion exchange activity J. Physiol. PubMed Scopus Google Scholar, J. Physiol. PubMed Scopus Google Scholar). The presence of the of AE1 transport activity ± 1% that the of AE1 transport activity by CAIV was on the catalytic activity of The of V143Y CAII also transport activity of AE2 and AE3 ± and 35 ± 1% inhibition, also that of CAIV with V143Y CAII AE2 and AE3 transport activity to full ± and 108 ± which a functional interaction with bicarbonate transport by AE2 and AE3. HEK293 transfected with AE2 AE3 and with V143Y CAII and CAIV the of the exchange activity was and expressed to the rate AE2 and AE3 the ± and the CAIV on the extracellular surface of cells, anchored a and has been to in the plasma A. Sly W.S. G. Biochem. Biophys. 1992; PubMed Scopus Google Scholar). of with Triton X-100 whereas the of the Cell. 1992; Full Text PDF PubMed Scopus Google Scholar). sucrose allows of proteins to We to the of a physical interaction between CAIV and AE1. HEK293 transfected with AE1 CAIV with AE1 and CAIV with Triton X-100 and sucrose a ultracentrifugation, and the of AE1 and CAIV in was that expressed CAIV is found predominantly in and but AE1 is expressed AE1 is found predominantly in However, AE1 and CAIV are AE1 predominantly in whereas the CAIV to The of CAIV a physical interaction between AE1 and The interaction between CAIV and AE was with a overlay Cell of HEK293 one of AE1, AE2, AE3 resolved by and to a with a cell of HEK293 with that CAIV was present to the of the AE in from HEK293 and to the a specific interaction of CAIV with only the AE present in that is a physical interaction between CAIV and the AE1, AE2, and AE3 anion exchange To the site of AE1 interaction with that CAIV interact with the extracellular of AE1. The a site are the extracellular of AE1, and GST fusion proteins of the third and fourth extracellular of AE1 in a GST pull-down GST and on and cell of transfected proteins in resolved on by to and In only in with from GST a of the CAIV revealed that more CAIV GST that CAIV to the fourth extracellular loop of to the fourth extracellular loop of of GST to the Cell of HEK293 transfected with CAIV transfected with to the and and the with resolved by on a to a and CAIV The the position of The that the expression of CAIV accelerates the rate of bicarbonate transport by AE1, AE2, and AE3. HEK293 CAII a that is to the bicarbonate transport activity of the AE family D. Reithmeier R.A. Casey J.R. J. Biol. Chem. 2001; 276: 47886-47894Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar). The of CAIV on AE transport was found only in the presence of V143Y CAII, which endogenous CAII from its binding site in AE, the anion transport rate D. Reithmeier R.A. Casey J.R. J. Biol. Chem. 2001; 276: 47886-47894Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar). bicarbonate transport by AE1, AE2, and AE3 was inhibited by by V143Y CAII, the of activity was by expression of The of AE activity by CAIV was blocked by a CA that the catalytic activity of CAIV was the of the AE bicarbonate transport Carbonic anhydrases and bicarbonate transport proteins are together bicarbonate and transport. showed that proteins form a complex (5Vince J.W. Reithmeier R.A.F. J. Biol. Chem. 1998; 273: 28430-28437Abstract Full Text Full Text PDF PubMed Scopus (212) Google Scholar, 6Vince J.W. Reithmeier R.A.F. Biochemistry. 2000; 39: 5527-5533Crossref PubMed Scopus (162) Google Scholar, 7Vince J.W. Carlsson U. Reithmeier R.A.F. Biochemistry. 2000; 39: 13344-13349Crossref PubMed Scopus (98) Google Scholar, G. A. A.K. J. Biol. 1993; PubMed Scopus Google Biochem. Biophys. 1989; PubMed Scopus Google and recently that the physical interaction between the AE family of bicarbonate transport proteins and CAII is activity D. Reithmeier R.A. Casey J.R. J. Biol. Chem. 2001; 276: 47886-47894Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar). The tissue distribution of CA isoforms the of the of the formation of a complex between bicarbonate transport proteins and other CA In the present the between the extracellular CA and plasma chloride/bicarbonate exchange of that CAIV and anion form a physical CAIV is to in the Cell. 1992; Full Text PDF PubMed Scopus Google Scholar). are in and and are to upon cell in Triton X-100 Cell. 1992; Full Text PDF PubMed Scopus Google Scholar). We the of CAIV in sucrose in the and presence of AE1. In the presence of AE1, the of CAIV from the is found expressed to the AE1 was that AE1 and CAIV interact and that AE1 CAIV of In a AE1, AE2, and AE3 expressed in HEK293 to interact with CAIV from cell of HEK293 CAIV in overlay The third and of a interaction from GST pull-down CAIV is to the extracellular surface of the that the interaction one of the extracellular of AE1. We the extracellular between and and and GST fusion proteins of the and GST fusion proteins and GST on from HEK293 transfected with CAIV with the GST CAIV associated with the was on The presence of a to the of CAIV only from to that CAIV to the fourth extracellular loop of AE1. the of of conclude that CAIV a complex with AE1, AE2, and AE3. The is that CAIV interacts with AE1, AE2, and AE3. We the that is to the However, the of is because CAII interacts with D. Reithmeier R.A. Casey J.R. J. Biol. Chem. 2001; 276: 47886-47894Abstract Full Text Full Text PDF PubMed Scopus (315) Google and to expressed in HEK293 cells. The of AE1, AE2, and AE3 bicarbonate transport activity by CAIV a interaction between CAIV and of CAIV to the may not to bicarbonate transport rate. The of the binding site CAIV is in a of of AE1 that is the extracellular loop J. Kopito Casey J.R. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar, R.A.F. S.L. M. in and and to form extracellular binding extracellular is by the blood the S.M. M.E. S. PubMed Google and D. J. M.E. 1998; PubMed Google which are found in The is by a complex between the A and AE1 S.M. M.E. S. PubMed Google Scholar). is interaction between and the extracellular of A of the AE1 from the site suggested that the a that was to whereas the with J. Kopito Casey J.R. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar). together that CAIV interacts with AE1 in the has been suggested to form the that to and from the transport site J. Kopito Casey J.R. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar). of CAIV to the to the extracellular of the anion transport The of AE2 and AE3 from AE1 in that AE2 and AE3 are on and is in AE2 and AE3 D. S.L. Biochemistry. PubMed Scopus Google Scholar). is not whether AE2 and AE3 interact with CAIV in the loop the of AE2 and AE3 bicarbonate transport activity in the presence of V143Y CAII a functional interaction between CAIV and AE2 and AE3, which is also by a physical We the of a transport metabolon by the of the physical and functional interaction between and CAII D. Reithmeier R.A. Casey J.R. J. Biol. Chem. 2001; 276: 47886-47894Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar). The present that the CAIV is the extracellular component of the bicarbonate transport metabolon. The presence of intracellular CAII and extracellular CAIV catalytic activity in the cell and the fact that potentiate the bicarbonate transport activity of AE1 the cell with a bicarbonate transport production of on the one of the the transport by AE and to on the other the by of the the transport by CA catalytic activity on of the plasma accelerates the AE-mediated bicarbonate transport shown in the heart not cytosolic extracellular CA one of which is to CAIV S. Sly W.S. G. J. 1998; PubMed Scopus Google Scholar). The heart also AE1, AE2, and AE3 S.C. Kudrycki K.E. Schull G.E. J. Biol. Chem. 1992; 267: 7927-7935Abstract Full Text PDF PubMed Google Scholar, S.C. G.E. PubMed Scopus Google Scholar, M. I. Vassort G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google which shown to interaction with CAII transport activity to D. Reithmeier R.A. Casey J.R. J. Biol. Chem. 2001; 276: 47886-47894Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar). that extracellular CAIV functionally the of CAII in bicarbonate to to their rate. The kidney truncated of AE1 is that localizes to the surface of S. D. Am. J. Physiol. 2001; PubMed Google is also one that is found the surface of J. J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar). AE2 is found in the surface of of the kidney K. A.K. S.L. Am. J. Physiol. Google Scholar). CAIV has been to in and of the S. Am. J. Physiol. 2000; Scholar, J. T. Waheed A. Sly W.S. Am. J. Physiol. 1999; 276: Google and the surface of the D. Sly W.S. Proc. Natl. Acad. Sci. U. S. A. 1990; PubMed Scopus Google but that CAIV is only found in the kidney G. Physiol. PubMed Scopus Google Scholar). AE1 and AE2 with CAIV in cells. CAII is by and W.S. D. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). associated with the of CAII, CA activity in erythrocytes is and Sly W.S. J. Physiol. 1988; PubMed Scopus Google Scholar). The in the present with the of CAIV expression and activity in human erythrocytes C.W. I. Physiol. 1999; PubMed Scopus Google the of erythrocytes CAII to AE2 in CAII AE2, to CAIV is not expressed in of from a to bicarbonate from the is that CAIV and AE interact in the the presence of functional CAIV in is not to of a physical interaction of extracellular CAIV with the Cl−/HCO3− transport We also that the presence CAIV catalytic activity accelerates the of bicarbonate the plasma by AE1, AE2, and AE3. The that CAIV is the extracellular component of a bicarbonate transport metabolon, with anion exchange and intracellular CAII and CAIV to the of AE, a bicarbonate the plasma The of AE transport activity by CAIV in the may the that the and transport. also a of of bicarbonate transport and the that of the with a to bicarbonate transport. We to the of CAIV and and also to the V143Y CAII

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