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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

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PtdIns4P en la red dispersada trans-Golgi media la activación del inflamatorio NLRP3

Jueqi Chen¹, Zhijian J Chen^2,3

¹Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

|November 30, 2018

Resumen

Diversos estímulos activan el inflamatorio NLRP3 mediante el desmontaje de la red trans-Golgi (TGN). NLRP3 se une a la TGN, se agrega y activa las vías de señalización inflamatoria.

Área de la Ciencia:

Inmunología
Biología celular
Biología molecular

Sus antecedentes:

El inflamatorio NLRP3 está implicado en varias enfermedades inflamatorias humanas.
Los mecanismos precisos por los cuales diversos estímulos activan NLRP3 siguen siendo en gran medida desconocidos.

Objetivo del estudio:

Para aclarar los eventos celulares tempranos y las interacciones moleculares que rigen la activación del inflamatorio NLRP3 por diferentes estímulos.

Principales métodos:

Investigó el papel de la red trans-Golgi (TGN) en la activación de NLRP3.
Se utilizaron ensayos bioquímicos para estudiar la interacción entre el NLRP3 y el fosfatidilinositol-4-fosfato (PtdIns4P).
Se observa la agregación de NLRP3 y la señalización posterior en respuesta a los estímulos.

Principales resultados:

Diversos estímulos NLRP3 inducen el desmontaje de la TGN en una TGN dispersa (dTGN).
NLRP3 se recluta a la dTGN a través de interacciones iónicas entre su región polibásica y PtdIns4P.
El dTGN actúa como un andamio para la agregación NLRP3, promoviendo la polimerización ASC y la señalización aguas abajo.
La interrupción de la interacción NLRP3-PtdIns4P anula la activación de NLRP3.

Conclusiones:

El reclutamiento de NLRP3 a la dTGN es un paso crítico y conservado en su activación por varios estímulos.
Este mecanismo dependiente de TGN proporciona un modelo unificado para comprender el ensamblaje y la activación del inflamatorio NLRP3.

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