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NEK7 es un mediador esencial de la activación de NLRP3 aguas abajo del eflujo de potasio

Yuan He¹, Melody Y Zeng¹, Dahai Yang^1,2

¹Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.

|January 28, 2016

Resumen

NEK7 se identifica como una proteína crucial para la activación del inflamatorio NLRP3, que actúa aguas abajo del eflujo de potasio para regular la activación inflamatoria de la caspasa-1 y la liberación de IL-1β en enfermedades inflamatorias.

Área de la Ciencia:

Inmunología
Biología molecular
Biología celular

Sus antecedentes:

Los inflamasomas son complejos de proteínas que activan las caspasas inflamatorias.
El inflamatorio NLRP3 está implicado en enfermedades inflamatorias y CAPS.
El eflujo de potasio es esencial para la activación de NLRP3, pero el mecanismo es desconocido.

Objetivo del estudio:

Identificar el mecanismo molecular de la activación del inflamatorio NLRP3 aguas abajo del eflujo de potasio.
Investigar el papel de NEK7 en el ensamblaje y la activación del inflamatorio NLRP3.

Principales métodos:

Identificación de NEK7 como una proteína que se une al NLRP3.
Evaluación de la activación de la caspasa-1 y la liberación de IL-1β en las células deficientes de NEK7.
Análisis de la formación del complejo NLRP3-NEK7 y la oligomerización de ASC.
Utilizando quimeras de ratón con células hematopoyéticas de tipo salvaje y knockout.

Principales resultados:

NEK7 se une a NLRP3 aguas abajo del eflujo de potasio, mediando la oligomerización y activación de NLRP3.
La deficiencia de NEK7 anula la activación de la caspasa-1 y la liberación de IL-1β para los estímulos NLRP3, pero no NLRC4 o AIM2.
NEK7 es esencial para la activación del inflamatorio NLRP3 en los macrófagos e in vivo.
La actividad catalítica de NEK7 es prescindible para la activación del inflamatorio NLRP3.

Conclusiones:

NEK7 es un componente esencial aguas abajo del eflujo de potasio para el ensamblaje y la activación del inflamatorio NLRP3.
NEK7 juega un papel crítico en las respuestas inflamatorias mediadas por el inflamatorio NLRP3.
Dirigirse a NEK7 podría ofrecer estrategias terapéuticas para las enfermedades inflamatorias impulsadas por NLRP3.

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