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El supercomplejo GPCR-G proteína-β-arrestina media la señalización sostenida de la proteína G

Alex R B Thomsen¹, Bianca Plouffe², Thomas J Cahill³

¹Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.

|August 9, 2016

Resumen

Los investigadores descubrieron nuevos "megaplejos" donde un solo receptor acoplado a proteínas G (GPCR) se une simultáneamente a una proteína G y a la β-arrestina dentro de las células. Este hallazgo explica la señalización sostenida de los GPCR internalizados.

Área de la Ciencia:

Biología celular
Farmacología molecular
La biofísica

Sus antecedentes:

La señalización del receptor acoplado a proteínas G (GPCR) ocurre tradicionalmente en la membrana plasmática, seguida de desensibilización e internalización.
La evidencia emergente sugiere que los GPCR pueden señalar desde compartimentos internalizados, lo que lleva a respuestas celulares sostenidas.

Objetivo del estudio:

Demostrar la existencia y la estructura de complejos de GPCR-G proteína-β-arrestina internalizados.
Para aclarar el mecanismo detrás de la señalización sostenida de GPCR desde ubicaciones intracelulares.

Principales métodos:

Ensayos bioquímicos
Técnicas biofísicas
Ensayos basados en células
Microscopía electrónica de una sola partícula

Principales resultados:

Se han identificado y caracterizado "megaplejos" que comprenden un solo GPCR, β-arrestina y proteína G dentro de compartimentos internalizados.
Se observó que la formación de megaplejos es favorecida por fuertes interacciones GPCR-β-arrestina, particularmente aquellas que involucran colas C-terminales fosforiladas.
La microscopía electrónica de partícula única reveló la unión simultánea del núcleo GPCR a la proteína G y el extremo C fosforilado a la β-arrestina.

Conclusiones:

La formación de megaplejos de proteínas GPCR-β-arrestina-G proporciona una base estructural para la señalización sostenida de los GPCR internalizados.
Este mecanismo desafía la visión clásica de la terminación de la señalización GPCR al momento de la internalización.

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