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Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation
Published on: September 7, 2010
El ectodominio del receptor 9 de tipo Toll se divide para generar un receptor funcional
Sarah E Ewald1, Bettina L Lee, Laura Lau
1Division of Immunology & Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, 405 Life Sciences Addition, Berkeley, California 94720-3200, USA.
Nature
|September 30, 2008
Resumen
Los receptores tipo peaje (TLR) 7 y 9 se procesan en los endolisosomas, con la escisión del ectodominio activando su función inmune. Esta escisión impide el reconocimiento del ácido nucleico, evitando la autoinmunidad.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Los receptores tipo Toll de mamíferos (TLRs) 3, 7, 8 y 9 reconocen los ácidos nucleicos microbianos para iniciar respuestas inmunes.
- El reconocimiento desregulado de los ácidos nucleicos por los TLR puede conducir a la autoinmunidad.
- Los mecanismos precisos de transporte y localización celular que rigen la función de TLR7 y TLR9 siguen sin estar claros.
Objetivo del estudio:
- Para dilucidar la vía de transporte intracelular de TLR9 y TLR7 desde el retículo endoplasmático hasta los endolisosomas.
- Investigar el procesamiento y las consecuencias funcionales de la escisión del ectodominio TLR9 y TLR7 dentro de los endolisosomas.
Principales métodos:
- Utilizó macrófagos de ratón y células dendríticas para rastrear el tráfico de TLR9 y TLR7.
- Se analizó la escisión del ectodominio del receptor en los compartimentos endolisomales.
- Evaluó las capacidades de unión de ligandos y reclutamiento de MyD88 de formas TLR9 de longitud completa frente a formas TLR9 escindidas.
Principales resultados:
- Se ha definido la ruta de transporte de TLR9 y TLR7 a los endolisosomas en las células inmunes.
- Se demostró que los ectodominios TLR9 y TLR7 se dividen proteolíticamente dentro de los endolisosomas.
- Identificó la forma escindida de TLR9, no la de longitud completa, como el receptor funcional que recluta a MyD88.8.
- Se ha demostrado que evitar la escisión o forzar la localización de la superficie hace que TLR9 no sea funcional.
Conclusiones:
- La escisión del ectodominio de TLR9 y TLR7 es esencial para su función en los endolisosomas.
- Este mecanismo de escisión restringe la activación del receptor a los compartimentos endolisomales.
- La escisión sirve como una estrategia reguladora crítica para prevenir las respuestas mediadas por TLR a los ácidos nucleicos y mantener la tolerancia inmune.
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