Intracellular Ca2+ oscillations generated via the extracellular Ca2+-sensing receptor (CaSR) in response to extracellular Ca2+ or l-phenylalanine: Impact of the highly conservative...
- Autores
- Young, Steven H.; Rey, Osvaldo; Rozengurt, Enrique
- Año de publicación
- 2015
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- The extracellular Ca2+-sensing receptor (CaSR) is an allosteric protein that responds to changes in the extracellular concentration of Ca2+ ([Ca2+]e) and aromatic amino acids with the production of different patterns of oscillations in intracellular Ca2+ concentration ([Ca2+]i). An increase in [Ca2+]e stimulates sinusoidal oscillations in [Ca2+]i whereas aromatic amino acid-induced CaR activation in the presence of a threshold [Ca2+]e promotes transient oscillations in [Ca2+]i. Here, we examined spontaneous and ligand-evoked [Ca2+]i oscillations in single HEK-293 cells transfected with the wild type CaSR or with a mutant CaSR in which Ser170 was converted to Thr (CaSRS170T). Our analysis demonstrates that cells expressing CaSRS170T display [Ca2+]i oscillations in the presence of low concentrations of extracellular Ca2+ and respond to L-Phe with robust transient [Ca2+]i oscillations. Our results indicate that the S170T mutation induces a marked increase in CaSR sensitivity to [Ca2+]e and imply that the allosteric regulation of the CaSR by aromatic amino acids is not only mediated by an heterotropic positive effect on Ca2+ binding cooperativity but, as biased agonists, aromatic amino acids stabilize a CaSR conformation that couples to a different signaling pathway leading to transient [Ca2+]i oscillations.
Fil: Young, Steven H.. University of California at Los Angeles; Estados Unidos
Fil: Rey, Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Rozengurt, Enrique. Veterans Affairs West Los Angeles Healthcare System; Estados Unidos. University of California at Los Angeles; Estados Unidos - Materia
-
Calcium sensing receptor
GPCR
Calcium oscillations
signal transduction - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/94909
Ver los metadatos del registro completo
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Intracellular Ca2+ oscillations generated via the extracellular Ca2+-sensing receptor (CaSR) in response to extracellular Ca2+ or l-phenylalanine: Impact of the highly conservative mutation Ser170ThrYoung, Steven H.Rey, OsvaldoRozengurt, EnriqueCalcium sensing receptorGPCRCalcium oscillationssignal transductionhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The extracellular Ca2+-sensing receptor (CaSR) is an allosteric protein that responds to changes in the extracellular concentration of Ca2+ ([Ca2+]e) and aromatic amino acids with the production of different patterns of oscillations in intracellular Ca2+ concentration ([Ca2+]i). An increase in [Ca2+]e stimulates sinusoidal oscillations in [Ca2+]i whereas aromatic amino acid-induced CaR activation in the presence of a threshold [Ca2+]e promotes transient oscillations in [Ca2+]i. Here, we examined spontaneous and ligand-evoked [Ca2+]i oscillations in single HEK-293 cells transfected with the wild type CaSR or with a mutant CaSR in which Ser170 was converted to Thr (CaSRS170T). Our analysis demonstrates that cells expressing CaSRS170T display [Ca2+]i oscillations in the presence of low concentrations of extracellular Ca2+ and respond to L-Phe with robust transient [Ca2+]i oscillations. Our results indicate that the S170T mutation induces a marked increase in CaSR sensitivity to [Ca2+]e and imply that the allosteric regulation of the CaSR by aromatic amino acids is not only mediated by an heterotropic positive effect on Ca2+ binding cooperativity but, as biased agonists, aromatic amino acids stabilize a CaSR conformation that couples to a different signaling pathway leading to transient [Ca2+]i oscillations.Fil: Young, Steven H.. University of California at Los Angeles; Estados UnidosFil: Rey, Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Rozengurt, Enrique. Veterans Affairs West Los Angeles Healthcare System; Estados Unidos. University of California at Los Angeles; Estados UnidosAcademic Press Inc Elsevier Science2015-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/94909Young, Steven H.; Rey, Osvaldo; Rozengurt, Enrique; Intracellular Ca2+ oscillations generated via the extracellular Ca2+-sensing receptor (CaSR) in response to extracellular Ca2+ or l-phenylalanine: Impact of the highly conservative mutation Ser170Thr; Academic Press Inc Elsevier Science; Biochemical and Biophysical Research Communications; 467; 1; 11-2015; 1-60006-291XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbrc.2015.09.144info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0006291X15306604info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:34:17Zoai:ri.conicet.gov.ar:11336/94909instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:34:17.592CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Intracellular Ca2+ oscillations generated via the extracellular Ca2+-sensing receptor (CaSR) in response to extracellular Ca2+ or l-phenylalanine: Impact of the highly conservative mutation Ser170Thr |
title |
Intracellular Ca2+ oscillations generated via the extracellular Ca2+-sensing receptor (CaSR) in response to extracellular Ca2+ or l-phenylalanine: Impact of the highly conservative mutation Ser170Thr |
spellingShingle |
Intracellular Ca2+ oscillations generated via the extracellular Ca2+-sensing receptor (CaSR) in response to extracellular Ca2+ or l-phenylalanine: Impact of the highly conservative mutation Ser170Thr Young, Steven H. Calcium sensing receptor GPCR Calcium oscillations signal transduction |
title_short |
Intracellular Ca2+ oscillations generated via the extracellular Ca2+-sensing receptor (CaSR) in response to extracellular Ca2+ or l-phenylalanine: Impact of the highly conservative mutation Ser170Thr |
title_full |
Intracellular Ca2+ oscillations generated via the extracellular Ca2+-sensing receptor (CaSR) in response to extracellular Ca2+ or l-phenylalanine: Impact of the highly conservative mutation Ser170Thr |
title_fullStr |
Intracellular Ca2+ oscillations generated via the extracellular Ca2+-sensing receptor (CaSR) in response to extracellular Ca2+ or l-phenylalanine: Impact of the highly conservative mutation Ser170Thr |
title_full_unstemmed |
Intracellular Ca2+ oscillations generated via the extracellular Ca2+-sensing receptor (CaSR) in response to extracellular Ca2+ or l-phenylalanine: Impact of the highly conservative mutation Ser170Thr |
title_sort |
Intracellular Ca2+ oscillations generated via the extracellular Ca2+-sensing receptor (CaSR) in response to extracellular Ca2+ or l-phenylalanine: Impact of the highly conservative mutation Ser170Thr |
dc.creator.none.fl_str_mv |
Young, Steven H. Rey, Osvaldo Rozengurt, Enrique |
author |
Young, Steven H. |
author_facet |
Young, Steven H. Rey, Osvaldo Rozengurt, Enrique |
author_role |
author |
author2 |
Rey, Osvaldo Rozengurt, Enrique |
author2_role |
author author |
dc.subject.none.fl_str_mv |
Calcium sensing receptor GPCR Calcium oscillations signal transduction |
topic |
Calcium sensing receptor GPCR Calcium oscillations signal transduction |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
The extracellular Ca2+-sensing receptor (CaSR) is an allosteric protein that responds to changes in the extracellular concentration of Ca2+ ([Ca2+]e) and aromatic amino acids with the production of different patterns of oscillations in intracellular Ca2+ concentration ([Ca2+]i). An increase in [Ca2+]e stimulates sinusoidal oscillations in [Ca2+]i whereas aromatic amino acid-induced CaR activation in the presence of a threshold [Ca2+]e promotes transient oscillations in [Ca2+]i. Here, we examined spontaneous and ligand-evoked [Ca2+]i oscillations in single HEK-293 cells transfected with the wild type CaSR or with a mutant CaSR in which Ser170 was converted to Thr (CaSRS170T). Our analysis demonstrates that cells expressing CaSRS170T display [Ca2+]i oscillations in the presence of low concentrations of extracellular Ca2+ and respond to L-Phe with robust transient [Ca2+]i oscillations. Our results indicate that the S170T mutation induces a marked increase in CaSR sensitivity to [Ca2+]e and imply that the allosteric regulation of the CaSR by aromatic amino acids is not only mediated by an heterotropic positive effect on Ca2+ binding cooperativity but, as biased agonists, aromatic amino acids stabilize a CaSR conformation that couples to a different signaling pathway leading to transient [Ca2+]i oscillations. Fil: Young, Steven H.. University of California at Los Angeles; Estados Unidos Fil: Rey, Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Rozengurt, Enrique. Veterans Affairs West Los Angeles Healthcare System; Estados Unidos. University of California at Los Angeles; Estados Unidos |
description |
The extracellular Ca2+-sensing receptor (CaSR) is an allosteric protein that responds to changes in the extracellular concentration of Ca2+ ([Ca2+]e) and aromatic amino acids with the production of different patterns of oscillations in intracellular Ca2+ concentration ([Ca2+]i). An increase in [Ca2+]e stimulates sinusoidal oscillations in [Ca2+]i whereas aromatic amino acid-induced CaR activation in the presence of a threshold [Ca2+]e promotes transient oscillations in [Ca2+]i. Here, we examined spontaneous and ligand-evoked [Ca2+]i oscillations in single HEK-293 cells transfected with the wild type CaSR or with a mutant CaSR in which Ser170 was converted to Thr (CaSRS170T). Our analysis demonstrates that cells expressing CaSRS170T display [Ca2+]i oscillations in the presence of low concentrations of extracellular Ca2+ and respond to L-Phe with robust transient [Ca2+]i oscillations. Our results indicate that the S170T mutation induces a marked increase in CaSR sensitivity to [Ca2+]e and imply that the allosteric regulation of the CaSR by aromatic amino acids is not only mediated by an heterotropic positive effect on Ca2+ binding cooperativity but, as biased agonists, aromatic amino acids stabilize a CaSR conformation that couples to a different signaling pathway leading to transient [Ca2+]i oscillations. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-11 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/94909 Young, Steven H.; Rey, Osvaldo; Rozengurt, Enrique; Intracellular Ca2+ oscillations generated via the extracellular Ca2+-sensing receptor (CaSR) in response to extracellular Ca2+ or l-phenylalanine: Impact of the highly conservative mutation Ser170Thr; Academic Press Inc Elsevier Science; Biochemical and Biophysical Research Communications; 467; 1; 11-2015; 1-6 0006-291X CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/94909 |
identifier_str_mv |
Young, Steven H.; Rey, Osvaldo; Rozengurt, Enrique; Intracellular Ca2+ oscillations generated via the extracellular Ca2+-sensing receptor (CaSR) in response to extracellular Ca2+ or l-phenylalanine: Impact of the highly conservative mutation Ser170Thr; Academic Press Inc Elsevier Science; Biochemical and Biophysical Research Communications; 467; 1; 11-2015; 1-6 0006-291X CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbrc.2015.09.144 info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0006291X15306604 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Academic Press Inc Elsevier Science |
publisher.none.fl_str_mv |
Academic Press Inc Elsevier Science |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1844613060366434304 |
score |
13.070432 |