Heteromerization Between the Bradykinin B 2 Receptor and the Angiotensin-(1-7) Mas Receptor Novelty and Significance

Autores
Cerrato, Bruno Diego; Carretero, Oscar A.; Janic, Brana; Grecco, Hernan Edgardo; Gironacci, Mariela Mercedes
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Bradykinin B2 receptor (B2R) and angiotensin-(1–7) Mas receptor (MasR)–mediated effects are physiologically interconnected. The molecular basis for such cross talk is unknown. It is hypothesized that the cross talk occurs at the receptor level. We investigated B2R–MasR heteromerization and the functional consequences of such interaction. B2R fused to the cyan fluorescent protein and MasR fused to the yellow fluorescent protein were transiently coexpressed in human embryonic kidney293T cells. Fluorescence resonance energy transfer analysis showed that B2R and MasR formed a constitutive heteromer, which was not modified by their agonists. B2R or MasR antagonists decreased fluorescence resonance energy transfer efficiency, suggesting that the antagonist promoted heteromer dissociation. B2R–MasR heteromerization induced an 8-fold increase in the MasR ligand-binding affinity. On agonist stimulation, the heteromer was internalized into early endosomes with a slower sequestration rate from the plasma membrane, compared with single receptors. B2R–MasR heteromerization induced a greater increase in arachidonic acid release and extracellular signal–regulated kinase phosphorylation after angiotensin-(1–7) stimulation, and this effect was blocked by the B2R antagonist. Concerning serine/threonine kinase Akt activity, a significant bradykinin-promoted activation was detected in B2R–MasR but not in B2R-expressing cells. Angiotensin-(1–7) and bradykinin elicited antiproliferative effects only in cells expressing B2R–MasR heteromers, but not in cells expressing each receptor alone. Proximity ligation assay confirmed B2R–MasR interaction in human glomerular endothelial cells supporting the interaction between both receptors in vivo. Our findings provide an explanation for the cross talk between bradykinin B2R and angiotensin-(1–7) MasR–mediated effects. B2R–MasR heteromerization induces functional changes in the receptor that may lead to long-lasting protective properties.
Fil: Cerrato, Bruno Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Carretero, Oscar A.. Henry Ford Hospital; Estados Unidos
Fil: Janic, Brana. Henry Ford Hospital; Estados Unidos
Fil: Grecco, Hernan Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina
Fil: Gironacci, Mariela Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Materia
B2 Receptor
Heteromerization
Internalization
Mas Receptor
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/47238
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/47238
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Heteromerization Between the Bradykinin B 2 Receptor and the Angiotensin-(1-7) Mas Receptor Novelty and SignificanceCerrato, Bruno DiegoCarretero, Oscar A.Janic, BranaGrecco, Hernan EdgardoGironacci, Mariela MercedesB2 ReceptorHeteromerizationInternalizationMas Receptorhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Bradykinin B2 receptor (B2R) and angiotensin-(1–7) Mas receptor (MasR)–mediated effects are physiologically interconnected. The molecular basis for such cross talk is unknown. It is hypothesized that the cross talk occurs at the receptor level. We investigated B2R–MasR heteromerization and the functional consequences of such interaction. B2R fused to the cyan fluorescent protein and MasR fused to the yellow fluorescent protein were transiently coexpressed in human embryonic kidney293T cells. Fluorescence resonance energy transfer analysis showed that B2R and MasR formed a constitutive heteromer, which was not modified by their agonists. B2R or MasR antagonists decreased fluorescence resonance energy transfer efficiency, suggesting that the antagonist promoted heteromer dissociation. B2R–MasR heteromerization induced an 8-fold increase in the MasR ligand-binding affinity. On agonist stimulation, the heteromer was internalized into early endosomes with a slower sequestration rate from the plasma membrane, compared with single receptors. B2R–MasR heteromerization induced a greater increase in arachidonic acid release and extracellular signal–regulated kinase phosphorylation after angiotensin-(1–7) stimulation, and this effect was blocked by the B2R antagonist. Concerning serine/threonine kinase Akt activity, a significant bradykinin-promoted activation was detected in B2R–MasR but not in B2R-expressing cells. Angiotensin-(1–7) and bradykinin elicited antiproliferative effects only in cells expressing B2R–MasR heteromers, but not in cells expressing each receptor alone. Proximity ligation assay confirmed B2R–MasR interaction in human glomerular endothelial cells supporting the interaction between both receptors in vivo. Our findings provide an explanation for the cross talk between bradykinin B2R and angiotensin-(1–7) MasR–mediated effects. B2R–MasR heteromerization induces functional changes in the receptor that may lead to long-lasting protective properties.Fil: Cerrato, Bruno Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Carretero, Oscar A.. Henry Ford Hospital; Estados UnidosFil: Janic, Brana. Henry Ford Hospital; Estados UnidosFil: Grecco, Hernan Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Gironacci, Mariela Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaLippincott Williams2016-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/47238Cerrato, Bruno Diego; Carretero, Oscar A.; Janic, Brana; Grecco, Hernan Edgardo; Gironacci, Mariela Mercedes; Heteromerization Between the Bradykinin B 2 Receptor and the Angiotensin-(1-7) Mas Receptor Novelty and Significance; Lippincott Williams; Hypertension; 68; 4; 10-2016; 1039-10480194-911XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1161/HYPERTENSIONAHA.116.07874info:eu-repo/semantics/altIdentifier/url/http://hyper.ahajournals.org/content/68/4/1039info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016258/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:41Zoai:ri.conicet.gov.ar:11336/47238instacron: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:34982025-09-03 09:59:41.98CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Heteromerization Between the Bradykinin B 2 Receptor and the Angiotensin-(1-7) Mas Receptor Novelty and Significance
title Heteromerization Between the Bradykinin B 2 Receptor and the Angiotensin-(1-7) Mas Receptor Novelty and Significance
spellingShingle Heteromerization Between the Bradykinin B 2 Receptor and the Angiotensin-(1-7) Mas Receptor Novelty and Significance
Cerrato, Bruno Diego
B2 Receptor
Heteromerization
Internalization
Mas Receptor
title_short Heteromerization Between the Bradykinin B 2 Receptor and the Angiotensin-(1-7) Mas Receptor Novelty and Significance
title_full Heteromerization Between the Bradykinin B 2 Receptor and the Angiotensin-(1-7) Mas Receptor Novelty and Significance
title_fullStr Heteromerization Between the Bradykinin B 2 Receptor and the Angiotensin-(1-7) Mas Receptor Novelty and Significance
title_full_unstemmed Heteromerization Between the Bradykinin B 2 Receptor and the Angiotensin-(1-7) Mas Receptor Novelty and Significance
title_sort Heteromerization Between the Bradykinin B 2 Receptor and the Angiotensin-(1-7) Mas Receptor Novelty and Significance
dc.creator.none.fl_str_mv Cerrato, Bruno Diego
Carretero, Oscar A.
Janic, Brana
Grecco, Hernan Edgardo
Gironacci, Mariela Mercedes
author Cerrato, Bruno Diego
author_facet Cerrato, Bruno Diego
Carretero, Oscar A.
Janic, Brana
Grecco, Hernan Edgardo
Gironacci, Mariela Mercedes
author_role author
author2 Carretero, Oscar A.
Janic, Brana
Grecco, Hernan Edgardo
Gironacci, Mariela Mercedes
author2_role author
author
author
author
dc.subject.none.fl_str_mv B2 Receptor
Heteromerization
Internalization
Mas Receptor
topic B2 Receptor
Heteromerization
Internalization
Mas Receptor
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Bradykinin B2 receptor (B2R) and angiotensin-(1–7) Mas receptor (MasR)–mediated effects are physiologically interconnected. The molecular basis for such cross talk is unknown. It is hypothesized that the cross talk occurs at the receptor level. We investigated B2R–MasR heteromerization and the functional consequences of such interaction. B2R fused to the cyan fluorescent protein and MasR fused to the yellow fluorescent protein were transiently coexpressed in human embryonic kidney293T cells. Fluorescence resonance energy transfer analysis showed that B2R and MasR formed a constitutive heteromer, which was not modified by their agonists. B2R or MasR antagonists decreased fluorescence resonance energy transfer efficiency, suggesting that the antagonist promoted heteromer dissociation. B2R–MasR heteromerization induced an 8-fold increase in the MasR ligand-binding affinity. On agonist stimulation, the heteromer was internalized into early endosomes with a slower sequestration rate from the plasma membrane, compared with single receptors. B2R–MasR heteromerization induced a greater increase in arachidonic acid release and extracellular signal–regulated kinase phosphorylation after angiotensin-(1–7) stimulation, and this effect was blocked by the B2R antagonist. Concerning serine/threonine kinase Akt activity, a significant bradykinin-promoted activation was detected in B2R–MasR but not in B2R-expressing cells. Angiotensin-(1–7) and bradykinin elicited antiproliferative effects only in cells expressing B2R–MasR heteromers, but not in cells expressing each receptor alone. Proximity ligation assay confirmed B2R–MasR interaction in human glomerular endothelial cells supporting the interaction between both receptors in vivo. Our findings provide an explanation for the cross talk between bradykinin B2R and angiotensin-(1–7) MasR–mediated effects. B2R–MasR heteromerization induces functional changes in the receptor that may lead to long-lasting protective properties.
Fil: Cerrato, Bruno Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Carretero, Oscar A.. Henry Ford Hospital; Estados Unidos
Fil: Janic, Brana. Henry Ford Hospital; Estados Unidos
Fil: Grecco, Hernan Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina
Fil: Gironacci, Mariela Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
description Bradykinin B2 receptor (B2R) and angiotensin-(1–7) Mas receptor (MasR)–mediated effects are physiologically interconnected. The molecular basis for such cross talk is unknown. It is hypothesized that the cross talk occurs at the receptor level. We investigated B2R–MasR heteromerization and the functional consequences of such interaction. B2R fused to the cyan fluorescent protein and MasR fused to the yellow fluorescent protein were transiently coexpressed in human embryonic kidney293T cells. Fluorescence resonance energy transfer analysis showed that B2R and MasR formed a constitutive heteromer, which was not modified by their agonists. B2R or MasR antagonists decreased fluorescence resonance energy transfer efficiency, suggesting that the antagonist promoted heteromer dissociation. B2R–MasR heteromerization induced an 8-fold increase in the MasR ligand-binding affinity. On agonist stimulation, the heteromer was internalized into early endosomes with a slower sequestration rate from the plasma membrane, compared with single receptors. B2R–MasR heteromerization induced a greater increase in arachidonic acid release and extracellular signal–regulated kinase phosphorylation after angiotensin-(1–7) stimulation, and this effect was blocked by the B2R antagonist. Concerning serine/threonine kinase Akt activity, a significant bradykinin-promoted activation was detected in B2R–MasR but not in B2R-expressing cells. Angiotensin-(1–7) and bradykinin elicited antiproliferative effects only in cells expressing B2R–MasR heteromers, but not in cells expressing each receptor alone. Proximity ligation assay confirmed B2R–MasR interaction in human glomerular endothelial cells supporting the interaction between both receptors in vivo. Our findings provide an explanation for the cross talk between bradykinin B2R and angiotensin-(1–7) MasR–mediated effects. B2R–MasR heteromerization induces functional changes in the receptor that may lead to long-lasting protective properties.
publishDate 2016
dc.date.none.fl_str_mv 2016-10
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/11336/47238
Cerrato, Bruno Diego; Carretero, Oscar A.; Janic, Brana; Grecco, Hernan Edgardo; Gironacci, Mariela Mercedes; Heteromerization Between the Bradykinin B 2 Receptor and the Angiotensin-(1-7) Mas Receptor Novelty and Significance; Lippincott Williams; Hypertension; 68; 4; 10-2016; 1039-1048
0194-911X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/47238
identifier_str_mv Cerrato, Bruno Diego; Carretero, Oscar A.; Janic, Brana; Grecco, Hernan Edgardo; Gironacci, Mariela Mercedes; Heteromerization Between the Bradykinin B 2 Receptor and the Angiotensin-(1-7) Mas Receptor Novelty and Significance; Lippincott Williams; Hypertension; 68; 4; 10-2016; 1039-1048
0194-911X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1161/HYPERTENSIONAHA.116.07874
info:eu-repo/semantics/altIdentifier/url/http://hyper.ahajournals.org/content/68/4/1039
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016258/
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 Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
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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score 13.13397

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