MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2–Dependent PathwayNovelty and Significance

Autores
Cerniello, Flavia Micaela; Carretero, Oscar A.; Longo, Nadia Andrea; Cerrato, Bruno Diego; Santos, Robson A.; Grecco, Hernan Edgardo; Gironacci, Mariela Mercedes
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The MAS1 receptor (R) exerts protective effects in the brain, heart, vessels, and kidney. R trafficking plays a critical function in signal termination and propagation and in R resensitization. We examined MAS1R internalization and trafficking on agonist stimulation and the role of β-arrestin2 in the activation of ERK1/2 (extracellular signal-regulated kinase 1/2) and Akt after MAS1R stimulation. Human embryonic kidney 293T cells were transfected with the coding sequence for MAS1R-YFP (MAS1R fused to yellow fluorescent protein). MAS1R internalization was evaluated by measuring the MAS1R present in the plasma membrane after agonist stimulation using a ligand-binding assay. MAS1R trafficking was evaluated by its colocalization with trafficking markers. MAS1R internalization was blocked in the presence of shRNAcaveolin-1 and with dominant negatives for Eps15 (a protein involved in endocytosed Rs by clathrin-coated pits) and for dynamin. After stimulation, MAS1R colocalized with Rab11 - a slow recycling vesicle marker - and not with Rab4 - a fast recycling vesicle marker - or LysoTracker - a lysosome marker. Cells transfected with MAS1R showed an increase in Akt and ERK1/2 activation on angiotensin-(1-7) stimulation, which was blocked when the clathrin-coated pits pathway was blocked. Suppression of β-arrestin2 by shRNA reduced the angiotensin-(1-7)-induced ERK1/2 activation, whereas Akt activation was not modified. We conclude that on agonist stimulation, MAS1R is internalized through clathrin-coated pits and caveolae in a dynamin-dependent manner and is then slowly recycled back to the plasma membrane. MAS1R induced Akt and ERK1/2 activation from early endosomes, and the activation of ERK1/2 was mediated by β-arrestin2. Thus, MAS1R activity and density may be tightly controlled by the cell.
Fil: Cerniello, Flavia Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
Fil: Carretero, Oscar A.. Henry Ford Hospital; Estados Unidos
Fil: Longo, Nadia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
Fil: Cerrato, Bruno Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
Fil: Santos, Robson A.. Universidade Federal de Minas Gerais; Brasil
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 ; Argentina
Materia
Angiotensin-(1-7)
Arrestin
Endocytosis
Endosomes
Mas1 Receptor
Trafficking
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:11336/47350
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/47350
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2–Dependent PathwayNovelty and SignificanceCerniello, Flavia MicaelaCarretero, Oscar A.Longo, Nadia AndreaCerrato, Bruno DiegoSantos, Robson A.Grecco, Hernan EdgardoGironacci, Mariela MercedesAngiotensin-(1-7)ArrestinEndocytosisEndosomesMas1 ReceptorTraffickinghttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The MAS1 receptor (R) exerts protective effects in the brain, heart, vessels, and kidney. R trafficking plays a critical function in signal termination and propagation and in R resensitization. We examined MAS1R internalization and trafficking on agonist stimulation and the role of β-arrestin2 in the activation of ERK1/2 (extracellular signal-regulated kinase 1/2) and Akt after MAS1R stimulation. Human embryonic kidney 293T cells were transfected with the coding sequence for MAS1R-YFP (MAS1R fused to yellow fluorescent protein). MAS1R internalization was evaluated by measuring the MAS1R present in the plasma membrane after agonist stimulation using a ligand-binding assay. MAS1R trafficking was evaluated by its colocalization with trafficking markers. MAS1R internalization was blocked in the presence of shRNAcaveolin-1 and with dominant negatives for Eps15 (a protein involved in endocytosed Rs by clathrin-coated pits) and for dynamin. After stimulation, MAS1R colocalized with Rab11 - a slow recycling vesicle marker - and not with Rab4 - a fast recycling vesicle marker - or LysoTracker - a lysosome marker. Cells transfected with MAS1R showed an increase in Akt and ERK1/2 activation on angiotensin-(1-7) stimulation, which was blocked when the clathrin-coated pits pathway was blocked. Suppression of β-arrestin2 by shRNA reduced the angiotensin-(1-7)-induced ERK1/2 activation, whereas Akt activation was not modified. We conclude that on agonist stimulation, MAS1R is internalized through clathrin-coated pits and caveolae in a dynamin-dependent manner and is then slowly recycled back to the plasma membrane. MAS1R induced Akt and ERK1/2 activation from early endosomes, and the activation of ERK1/2 was mediated by β-arrestin2. Thus, MAS1R activity and density may be tightly controlled by the cell.Fil: Cerniello, Flavia Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; ArgentinaFil: Carretero, Oscar A.. Henry Ford Hospital; Estados UnidosFil: Longo, Nadia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; ArgentinaFil: Cerrato, Bruno Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; ArgentinaFil: Santos, Robson A.. Universidade Federal de Minas Gerais; BrasilFil: 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 ; ArgentinaLippincott Williams2017-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/47350Cerniello, Flavia Micaela; Carretero, Oscar A.; Longo, Nadia Andrea; Cerrato, Bruno Diego; Santos, Robson A.; et al.; MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2–Dependent PathwayNovelty and Significance; Lippincott Williams; Hypertension; 70; 5; 11-2017; 982-9890194-911XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1161/HYPERTENSIONAHA.117.09789info:eu-repo/semantics/altIdentifier/url/http://hyper.ahajournals.org/content/70/5/982info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5638701/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 Técnicas2025-09-10T13:18:20Zoai:ri.conicet.gov.ar:11336/47350instacron: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:34982025-09-10 13:18:21.053CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2–Dependent PathwayNovelty and Significance
title MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2–Dependent PathwayNovelty and Significance
spellingShingle MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2–Dependent PathwayNovelty and Significance
Cerniello, Flavia Micaela
Angiotensin-(1-7)
Arrestin
Endocytosis
Endosomes
Mas1 Receptor
Trafficking
title_short MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2–Dependent PathwayNovelty and Significance
title_full MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2–Dependent PathwayNovelty and Significance
title_fullStr MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2–Dependent PathwayNovelty and Significance
title_full_unstemmed MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2–Dependent PathwayNovelty and Significance
title_sort MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2–Dependent PathwayNovelty and Significance
dc.creator.none.fl_str_mv Cerniello, Flavia Micaela
Carretero, Oscar A.
Longo, Nadia Andrea
Cerrato, Bruno Diego
Santos, Robson A.
Grecco, Hernan Edgardo
Gironacci, Mariela Mercedes
author Cerniello, Flavia Micaela
author_facet Cerniello, Flavia Micaela
Carretero, Oscar A.
Longo, Nadia Andrea
Cerrato, Bruno Diego
Santos, Robson A.
Grecco, Hernan Edgardo
Gironacci, Mariela Mercedes
author_role author
author2 Carretero, Oscar A.
Longo, Nadia Andrea
Cerrato, Bruno Diego
Santos, Robson A.
Grecco, Hernan Edgardo
Gironacci, Mariela Mercedes
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Angiotensin-(1-7)
Arrestin
Endocytosis
Endosomes
Mas1 Receptor
Trafficking
topic Angiotensin-(1-7)
Arrestin
Endocytosis
Endosomes
Mas1 Receptor
Trafficking
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The MAS1 receptor (R) exerts protective effects in the brain, heart, vessels, and kidney. R trafficking plays a critical function in signal termination and propagation and in R resensitization. We examined MAS1R internalization and trafficking on agonist stimulation and the role of β-arrestin2 in the activation of ERK1/2 (extracellular signal-regulated kinase 1/2) and Akt after MAS1R stimulation. Human embryonic kidney 293T cells were transfected with the coding sequence for MAS1R-YFP (MAS1R fused to yellow fluorescent protein). MAS1R internalization was evaluated by measuring the MAS1R present in the plasma membrane after agonist stimulation using a ligand-binding assay. MAS1R trafficking was evaluated by its colocalization with trafficking markers. MAS1R internalization was blocked in the presence of shRNAcaveolin-1 and with dominant negatives for Eps15 (a protein involved in endocytosed Rs by clathrin-coated pits) and for dynamin. After stimulation, MAS1R colocalized with Rab11 - a slow recycling vesicle marker - and not with Rab4 - a fast recycling vesicle marker - or LysoTracker - a lysosome marker. Cells transfected with MAS1R showed an increase in Akt and ERK1/2 activation on angiotensin-(1-7) stimulation, which was blocked when the clathrin-coated pits pathway was blocked. Suppression of β-arrestin2 by shRNA reduced the angiotensin-(1-7)-induced ERK1/2 activation, whereas Akt activation was not modified. We conclude that on agonist stimulation, MAS1R is internalized through clathrin-coated pits and caveolae in a dynamin-dependent manner and is then slowly recycled back to the plasma membrane. MAS1R induced Akt and ERK1/2 activation from early endosomes, and the activation of ERK1/2 was mediated by β-arrestin2. Thus, MAS1R activity and density may be tightly controlled by the cell.
Fil: Cerniello, Flavia Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
Fil: Carretero, Oscar A.. Henry Ford Hospital; Estados Unidos
Fil: Longo, Nadia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
Fil: Cerrato, Bruno Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
Fil: Santos, Robson A.. Universidade Federal de Minas Gerais; Brasil
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 ; Argentina
description The MAS1 receptor (R) exerts protective effects in the brain, heart, vessels, and kidney. R trafficking plays a critical function in signal termination and propagation and in R resensitization. We examined MAS1R internalization and trafficking on agonist stimulation and the role of β-arrestin2 in the activation of ERK1/2 (extracellular signal-regulated kinase 1/2) and Akt after MAS1R stimulation. Human embryonic kidney 293T cells were transfected with the coding sequence for MAS1R-YFP (MAS1R fused to yellow fluorescent protein). MAS1R internalization was evaluated by measuring the MAS1R present in the plasma membrane after agonist stimulation using a ligand-binding assay. MAS1R trafficking was evaluated by its colocalization with trafficking markers. MAS1R internalization was blocked in the presence of shRNAcaveolin-1 and with dominant negatives for Eps15 (a protein involved in endocytosed Rs by clathrin-coated pits) and for dynamin. After stimulation, MAS1R colocalized with Rab11 - a slow recycling vesicle marker - and not with Rab4 - a fast recycling vesicle marker - or LysoTracker - a lysosome marker. Cells transfected with MAS1R showed an increase in Akt and ERK1/2 activation on angiotensin-(1-7) stimulation, which was blocked when the clathrin-coated pits pathway was blocked. Suppression of β-arrestin2 by shRNA reduced the angiotensin-(1-7)-induced ERK1/2 activation, whereas Akt activation was not modified. We conclude that on agonist stimulation, MAS1R is internalized through clathrin-coated pits and caveolae in a dynamin-dependent manner and is then slowly recycled back to the plasma membrane. MAS1R induced Akt and ERK1/2 activation from early endosomes, and the activation of ERK1/2 was mediated by β-arrestin2. Thus, MAS1R activity and density may be tightly controlled by the cell.
publishDate 2017
dc.date.none.fl_str_mv 2017-11
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/11336/47350
Cerniello, Flavia Micaela; Carretero, Oscar A.; Longo, Nadia Andrea; Cerrato, Bruno Diego; Santos, Robson A.; et al.; MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2–Dependent PathwayNovelty and Significance; Lippincott Williams; Hypertension; 70; 5; 11-2017; 982-989
0194-911X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/47350
identifier_str_mv Cerniello, Flavia Micaela; Carretero, Oscar A.; Longo, Nadia Andrea; Cerrato, Bruno Diego; Santos, Robson A.; et al.; MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2–Dependent PathwayNovelty and Significance; Lippincott Williams; Hypertension; 70; 5; 11-2017; 982-989
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.117.09789
info:eu-repo/semantics/altIdentifier/url/http://hyper.ahajournals.org/content/70/5/982
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5638701/
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
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 13.004268

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