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Los homólogos Lgr5 se asocian con los receptores Wnt y median la señalización de R-spondina
Wim de Lau1, Nick Barker, Teck Y Low
1Hubrecht Institute and University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Nature
|July 6, 2011
Resumen
El receptor acoplado a la proteína G rico en leucina 5 (Lgr5) y Lgr4 son componentes clave de la vía Wnt. La eliminación de estos genes perjudica la función de las células madre intestinales, pero las R-espondinas pueden mejorar la señalización de Wnt a través de Lgr4/5.5.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología del desarrollo Biología del desarrollo.
- Biología Molecular Biología Molecular
Sus antecedentes:
- El receptor acoplado a la proteína G rico en leucina 5 (Lgr5) y su homólogo Lgr4 se coexpresan en compartimentos proliferativos impulsados por Wnt.
- Estos receptores están implicados en la señalización de Wnt, crucial para el desarrollo y la regeneración de los tejidos.
Objetivo del estudio:
- Investigar las funciones funcionales de Lgr4 y Lgr5 en la vía de señalización Wnt intestinal del ratón.
- Para dilucidar el mecanismo por el cual las R-espondinas mejoran la señalización Wnt a través de los receptores Lgr.
Principales métodos:
- Eliminación condicional del gen Lgr4 y Lgr5 en criptas intestinales de ratón.
- Espectrometría de masas para identificar las interacciones de las proteínas.
- Ensayos celulares HEK293 para estudiar la modulación de la señalización Wnt por las proteínas R-spondinas y Lgr.
- Culturas de cripta intestinal de ratón para evaluar los efectos de la deleción de genes.
Principales resultados:
- La eliminación condicional de Lgr4 y Lgr5 en el intestino del ratón afecta la expresión génica objetivo de Wnt y conduce a la muerte de la cripta intestinal.
- Lgr4 y Lgr5 se asocian con el complejo de receptores Frizzled/Lrp Wnt.
- Las R-espondinas se unen a Lgr4, Lgr5 y Lgr6, mejorando las señales iniciadas por Wnt3a, una función dependiente de la presencia de Lgr4/5.
Conclusiones:
- Los homólogos de Lgr5 actúan como componentes facultativos del receptor Wnt, mediando la mejora de la señal de R-spondina.
- Estos hallazgos proporcionan información sobre las aplicaciones de la R-espondina para la medicina regenerativa en tejidos que expresan homólogos Lgr5.
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