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Wnt induce los señalosomas de LRP6 y promueve la fosforilación de LRP6 dependiente del desordenado
Josipa Bilic1, Ya-Lin Huang, Gary Davidson
1Division of Molecular Embryology, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Science (New York, N.Y.)
|June 16, 2007
Resumen
La señalización de Wnt desencadena la agregación y fosforilación de LRP6, formando los señalosomas. Este proceso es esencial para eventos posteriores como la estabilización de la beta-catenina en el desarrollo celular y el cáncer.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Biología del desarrollo Biología del desarrollo.
Sus antecedentes:
- La señalización Wnt es crucial para el desarrollo, las células madre y el cáncer.
- El mecanismo preciso de la activación del receptor Wnt sigue sin estar claro.
Objetivo del estudio:
- Para dilucidar el mecanismo de iniciación de la señalización Wnt en la membrana plasmática.
- Investigar el papel de la agregación LRP6 en la activación de la vía Wnt.
Principales métodos:
- Imágenes en vivo de las células de los vertebrados.
- Análisis bioquímico de los complejos LRP6.
- Utilizando Dishevelled (Dvl) como una proteína clave en la vía.
Principales resultados:
- El tratamiento con Wnt induce rápidamente agregados LRP6 asociados a la membrana plasmática.
- Los agregados LRP6 fosforilados forman complejos del tamaño de un ribosoma que contienen componentes de la vía Wnt.
- Se requiere desgarrado (Dvl) para la fosforilación y agregación de LRP6.
Conclusiones:
- Los Wnts inducen el receptor y el Dvl se coagulan en LRP6-signalosomes.
- Estos señalosomas desencadenan la fosforilación de LRP6, promoviendo el reclutamiento de axinas y la estabilización de la beta-catenina.
- Esto proporciona una nueva visión mecánica de la iniciación de la señal Wnt.
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