Artículo
MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2–Dependent PathwayNovelty and Significance
Cerniello, Flavia Micaela
; Carretero, Oscar A.; Longo, Nadia Andrea
; Cerrato, Bruno Diego
; Santos, Robson A.; Grecco, Hernan Edgardo
; Gironacci, Mariela Mercedes
Fecha de publicación:
11/2017
Editorial:
Lippincott Williams
Revista:
Hypertension
ISSN:
0194-911X
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
Angiotensin-(1-7)
,
Arrestin
,
Endocytosis
,
Endosomes
,
Mas1 Receptor
,
Trafficking
Archivos asociados
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Identificadores
Colecciones
Articulos(IFIBA)
Articulos de INST.DE FISICA DE BUENOS AIRES
Articulos de INST.DE FISICA DE BUENOS AIRES
Articulos(IQUIFIB)
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Citación
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
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