Obligatory amino acid exchange via systems b0,+ like and y+L-like. A tertiary active transport mechanism for renal re-absorption of cystine and diabsic amino acids

Mutations in the rBAT gene cause type I cystinuria, a common inherited aminoaciduria of cystine and dibasic amino acids due to their defective renal and intestinal reabsorption (Calonge, M. J., Gasparini, P., Chillarón, J., Chillón, M., Gallucci, M., Rousaud, F., Zelante, L., Testar, X., Dallapiccol...

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Autores: Chillarón Chaves, José Julio, Estévez Povedano, Raúl, Mora, Conchi, Wagner, Carsten A., Suessbrich, Hartmut, Lang, Florian, Gelpí Buchaca, Josep Lluís, Testar, Xavier, Busch, Andreas, Zorzano Olarte, Antonio, Palacín Prieto, Manuel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:1996
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/177609
Acceso en línea:https://hdl.handle.net/2445/177609
Access Level:acceso abierto
Palabra clave:Aminoàcids
Proteïnes portadores
Glicoproteïnes
Amino acids
Carrier proteins
Glycoproteins
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spelling Obligatory amino acid exchange via systems b0,+ like and y+L-like. A tertiary active transport mechanism for renal re-absorption of cystine and diabsic amino acidsChillarón Chaves, José JulioEstévez Povedano, RaúlMora, ConchiWagner, Carsten A.Suessbrich, HartmutLang, FlorianGelpí Buchaca, Josep LluísTestar, XavierBusch, AndreasZorzano Olarte, AntonioPalacín Prieto, ManuelAminoàcidsProteïnes portadoresGlicoproteïnesAmino acidsCarrier proteinsGlycoproteinsMutations in the rBAT gene cause type I cystinuria, a common inherited aminoaciduria of cystine and dibasic amino acids due to their defective renal and intestinal reabsorption (Calonge, M. J., Gasparini, P., Chillarón, J., Chillón, M., Gallucci, M., Rousaud, F., Zelante, L., Testar, X., Dallapiccola, B., Di Silverio, F., Barceló, P., Estivill, X., Zorzano, A., Nunes, V., and Palacín, M. (1994) Nat. Genet. 6, 420-426; Calonge, M. J., Volipini, V., Bisceglia, L., Rousaud, F., De Sanctis, L., Beccia, E., Zelante, L., Testar, X., Zorzano, A., Estivill, X., Gasparini, P., Nunes, V., and Palacín, M.(1995) Proc. Natl. Acad. Sci. U. S. A. 92, 9667-9671). One important question that remains to be clarified is how the apparently non-concentrative system bo,+-like, associated with rBAT expression, participates in the active renal reabsorption of these amino acids. Several studies have demonstrated exchange of amino acids induced by rBAT in Xenopus oocytes. Here we offer evidence that system bo,+-like is an obligatory amino acid exchanger in oocytes and in the 'renal proximal tubular' cell line OK. System bo, +-like showed a 1:1 stoichiometry of exchange, and the hetero-exchange dibasic (inward) with neutral (outward) amino acids were favored in oocytes. Obligatory exchange of amino acids via system bo,+-like fully explained the amino acid-induced current in rBAT-injected oocytes. Exchange via system bo,+-like is coupled enough to ensure a specific accumulation of substrates until the complete replacement of the internal oocyte substrates. Due to structural and functional analogies of the cell surface antigen 4F2hc to rBAT, we tested for amino acid exchange via system y+L-like. 4F2hc-injected oocytes accumulated substrates to a level higher than CAT1-injected oocytes (i.e. oocytes expressing system y+) and showed exchange of amino acids with the substrate specificity of system y+L and L-leucine-induced outward currents in the absence of extracellular sodium. In contrast to L-arginine, system y+L-like did not mediate measurable L-leucine efflux from the oocyte. We propose a role of systems bo,+-like and y+L-like in the renal reabsorption of cystine and dibasic amino acids that is based on their active tertiary transport mechanism and on the apical and basolateral localization of rBAT and 4F2hc, respectively, in the epithelial cells of the proximal tubule of the nephron.American Society for Biochemistry and Molecular Biology2021202119962021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion10 p.application/pdfhttps://hdl.handle.net/2445/177609Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1074/jbc.271.30.17761Journal of Biological Chemistry, 1996, vol. 271, num. 30, p. 17761-17770https://doi.org/10.1074/jbc.271.30.17761(c) American Society for Biochemistry and Molecular Biology, 1996info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1776092026-05-29T05:05:01Z
dc.title.none.fl_str_mv Obligatory amino acid exchange via systems b0,+ like and y+L-like. A tertiary active transport mechanism for renal re-absorption of cystine and diabsic amino acids
title Obligatory amino acid exchange via systems b0,+ like and y+L-like. A tertiary active transport mechanism for renal re-absorption of cystine and diabsic amino acids
spellingShingle Obligatory amino acid exchange via systems b0,+ like and y+L-like. A tertiary active transport mechanism for renal re-absorption of cystine and diabsic amino acids
Chillarón Chaves, José Julio
Aminoàcids
Proteïnes portadores
Glicoproteïnes
Amino acids
Carrier proteins
Glycoproteins
title_short Obligatory amino acid exchange via systems b0,+ like and y+L-like. A tertiary active transport mechanism for renal re-absorption of cystine and diabsic amino acids
title_full Obligatory amino acid exchange via systems b0,+ like and y+L-like. A tertiary active transport mechanism for renal re-absorption of cystine and diabsic amino acids
title_fullStr Obligatory amino acid exchange via systems b0,+ like and y+L-like. A tertiary active transport mechanism for renal re-absorption of cystine and diabsic amino acids
title_full_unstemmed Obligatory amino acid exchange via systems b0,+ like and y+L-like. A tertiary active transport mechanism for renal re-absorption of cystine and diabsic amino acids
title_sort Obligatory amino acid exchange via systems b0,+ like and y+L-like. A tertiary active transport mechanism for renal re-absorption of cystine and diabsic amino acids
dc.creator.none.fl_str_mv Chillarón Chaves, José Julio
Estévez Povedano, Raúl
Mora, Conchi
Wagner, Carsten A.
Suessbrich, Hartmut
Lang, Florian
Gelpí Buchaca, Josep Lluís
Testar, Xavier
Busch, Andreas
Zorzano Olarte, Antonio
Palacín Prieto, Manuel
author Chillarón Chaves, José Julio
author_facet Chillarón Chaves, José Julio
Estévez Povedano, Raúl
Mora, Conchi
Wagner, Carsten A.
Suessbrich, Hartmut
Lang, Florian
Gelpí Buchaca, Josep Lluís
Testar, Xavier
Busch, Andreas
Zorzano Olarte, Antonio
Palacín Prieto, Manuel
author_role author
author2 Estévez Povedano, Raúl
Mora, Conchi
Wagner, Carsten A.
Suessbrich, Hartmut
Lang, Florian
Gelpí Buchaca, Josep Lluís
Testar, Xavier
Busch, Andreas
Zorzano Olarte, Antonio
Palacín Prieto, Manuel
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Aminoàcids
Proteïnes portadores
Glicoproteïnes
Amino acids
Carrier proteins
Glycoproteins
topic Aminoàcids
Proteïnes portadores
Glicoproteïnes
Amino acids
Carrier proteins
Glycoproteins
description Mutations in the rBAT gene cause type I cystinuria, a common inherited aminoaciduria of cystine and dibasic amino acids due to their defective renal and intestinal reabsorption (Calonge, M. J., Gasparini, P., Chillarón, J., Chillón, M., Gallucci, M., Rousaud, F., Zelante, L., Testar, X., Dallapiccola, B., Di Silverio, F., Barceló, P., Estivill, X., Zorzano, A., Nunes, V., and Palacín, M. (1994) Nat. Genet. 6, 420-426; Calonge, M. J., Volipini, V., Bisceglia, L., Rousaud, F., De Sanctis, L., Beccia, E., Zelante, L., Testar, X., Zorzano, A., Estivill, X., Gasparini, P., Nunes, V., and Palacín, M.(1995) Proc. Natl. Acad. Sci. U. S. A. 92, 9667-9671). One important question that remains to be clarified is how the apparently non-concentrative system bo,+-like, associated with rBAT expression, participates in the active renal reabsorption of these amino acids. Several studies have demonstrated exchange of amino acids induced by rBAT in Xenopus oocytes. Here we offer evidence that system bo,+-like is an obligatory amino acid exchanger in oocytes and in the 'renal proximal tubular' cell line OK. System bo, +-like showed a 1:1 stoichiometry of exchange, and the hetero-exchange dibasic (inward) with neutral (outward) amino acids were favored in oocytes. Obligatory exchange of amino acids via system bo,+-like fully explained the amino acid-induced current in rBAT-injected oocytes. Exchange via system bo,+-like is coupled enough to ensure a specific accumulation of substrates until the complete replacement of the internal oocyte substrates. Due to structural and functional analogies of the cell surface antigen 4F2hc to rBAT, we tested for amino acid exchange via system y+L-like. 4F2hc-injected oocytes accumulated substrates to a level higher than CAT1-injected oocytes (i.e. oocytes expressing system y+) and showed exchange of amino acids with the substrate specificity of system y+L and L-leucine-induced outward currents in the absence of extracellular sodium. In contrast to L-arginine, system y+L-like did not mediate measurable L-leucine efflux from the oocyte. We propose a role of systems bo,+-like and y+L-like in the renal reabsorption of cystine and dibasic amino acids that is based on their active tertiary transport mechanism and on the apical and basolateral localization of rBAT and 4F2hc, respectively, in the epithelial cells of the proximal tubule of the nephron.
publishDate 1996
dc.date.none.fl_str_mv 1996
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/177609
url https://hdl.handle.net/2445/177609
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1074/jbc.271.30.17761
Journal of Biological Chemistry, 1996, vol. 271, num. 30, p. 17761-17770
https://doi.org/10.1074/jbc.271.30.17761
dc.rights.none.fl_str_mv (c) American Society for Biochemistry and Molecular Biology, 1996
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Society for Biochemistry and Molecular Biology, 1996
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 10 p.
application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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