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La fosforilación de la optineurina del receptor de la autofagia restringe el crecimiento de Salmonella
Philipp Wild1, Hesso Farhan, David G McEwan
1Frankfurt Institute for Molecular Life Sciences and Institute of Biochemistry II, Goethe University School of Medicine, Frankfurt (Main), Germany.
Science (New York, N.Y.)
|May 28, 2011
Resumen
La fosforilación de la optineurina del receptor de la autofagia por la TANK binding kinase 1 (TBK1) mejora el aclaramiento de la Salmonella citosólica. Este descubrimiento revela un mecanismo regulador clave para la autofagia selectiva en respuesta a la infección bacteriana.
Área de la Ciencia:
- Biología celular Biología celular.
- Inmunología Inmunología.
- Biología Molecular Biología Molecular
Sus antecedentes:
- La autofagia selectiva utiliza moléculas de receptores para vincular las cargas a las membranas autofagosómicas.
- Los mecanismos que controlan la función del receptor de la autofagia in vivo no se comprenden bien.
Objetivo del estudio:
- Para investigar el papel de la fosforilación de la optineurina en la autofagia selectiva.
- Para aclarar el mecanismo por el cual la TANK binding kinase 1 (TBK1) regula la función de la optineurina.
Principales métodos:
- Se utilizaron modelos in vivo para estudiar la fosforilación de la optineurina.
- Investigó la interacción entre TBK1, optineurina y LC3.
- Se evaluó el impacto de la manipulación de la optineurina y TBK1 en la autofagia de Salmonella.
Principales resultados:
- La fosforilación de la optineurina en la serina-177 por TBK1 mejora su unión a la LC3.
- Esta fosforilación promueve la autofagia selectiva de la Salmonella entérica citosólica cubierta de ubiquitina.
- El deterioro de la función de la optineurina o TBK1 condujo a una reducción de la autofagia por Salmonella y un aumento de la proliferación bacteriana.
Conclusiones:
- La fosforilación de la optineurina por TBK1 es un regulador crítico de la autofagia selectiva para las bacterias citosólicas.
- Este mecanismo mejora el aclaramiento de Salmonella mediante la promoción de la formación de autofagosomas.
- La fosforilación de los receptores de la autofagia puede representar una estrategia reguladora general para la autofagia selectiva de carga.
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