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Las proteínas de Kremen son receptores Dickkopf que regulan la señalización de Wnt/beta-catenina
Bingyu Mao1, Wei Wu, Gary Davidson
1Molecular Embryology Division, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Nature
|June 7, 2002
Resumen
Las proteínas Kremen1 y Kremen2 actúan como receptores para Dickkopf1 (Dkk1), inhibiendo la señalización de Wnt/beta-catenina. Estas proteínas de Kremen, junto con Dkk1, modulan el receptor LRP6 Wnt, afectando el crecimiento y la diferenciación celular.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología del desarrollo Biología del desarrollo.
- La señalización celular de las células.
Sus antecedentes:
- La señalización Wnt es crucial para el crecimiento y la diferenciación celular.
- La señalización canónica de Wnt implica la estabilización de la beta-catenina a través de los receptores Frizzled y LRP5/6.
- Dickkopf1 (Dkk1) inhibe la señalización de Wnt al unirse a LRP5/6.6.
Objetivo del estudio:
- Para identificar nuevos receptores para el Dickkopf1 (Dkk1).
- Investigar el papel de Kremen1 y Kremen2 en la señalización de Wnt/beta-catenina.
- Para dilucidar el mecanismo por el cual las proteínas Dkk1 y Kremen inhiben la señalización Wnt.
Principales métodos:
- Los ensayos de coinmunoprecipitación detectan complejos proteicos.
- Ensayos basados en células para medir la actividad de señalización de Wnt/beta-catenina.
- Microscopía confocal para visualizar la localización del receptor y la endocitosis.
Principales resultados:
- Kremen1 y Kremen2 fueron identificados como receptores Dkk1 de alta afinidad.
- Las proteínas de Kremen cooperan con Dkk1 para inhibir la señalización de Wnt/beta-catenina.
- Kremen2 forma un complejo ternario con Dkk1 y LRP6, promoviendo la endocitosis LRP6.
Conclusiones:
- Kremen1 y Kremen2 son componentes clave de un complejo inhibidor mediado por Dkk1 para la señalización Wnt.
- Este complejo modula la señalización canónica de Wnt regulando los niveles del receptor LRP6 en la membrana plasmática.
- Los hallazgos proporcionan nuevos conocimientos sobre la regulación de la señalización Wnt en los vertebrados.
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