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La p38 y una proteína que interactúa con la p38 son críticas para la regulación a la baja de la E-cadherina durante
Irene E Zohn1, Yingqiu Li, Edward Y Skolnik
1Howard Hughes Medical Institute, Department of Pediatrics, Section of Developmental Biology, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA.
Cell
|June 6, 2006
Resumen
La p38 MAP quinasa y la proteína que interactúa con la p38 (p38IP) son esenciales para la migración del mesodermo durante la gastrulación de los vertebrados mediante la regulación a la baja de la E-cadherina. Las mutaciones en p38IP interrumpen este proceso, causando defectos en el desarrollo.
Área de la Ciencia:
- Biología del desarrollo Biología del desarrollo.
- La señalización celular de las células.
- Genética molecular La genética molecular.
Sus antecedentes:
- La gastrulación de los vertebrados implica la transición epitelial a mesenquimal (EMT) para la migración del mesodermo.
- La regulación a la baja de la E-caderina es crítica para la EMT durante la gastrulación.
- El papel de la p38 MAP quinasa y sus proteínas que interactúan en este proceso requiere una mayor aclaración.
Objetivo del estudio:
- Para investigar el papel de la p38 MAP quinasa y la proteína que interactúa con la p38 (p38IP) en la regulación a la baja de la E-cadherina durante la gastrulación.
- Identificar los factores genéticos que afectan la función de p38IP y su impacto en el desarrollo embrionario.
Principales métodos:
- Pantalla de mutagenesis ENU para identificar las mutaciones que afectan a p38IP.
- Análisis de embriones mutantes (p38IP(drey, p38IP(RRK)) para detectar defectos en el desarrollo.
- Pruebas bioquímicas para determinar la interacción de p38IP con p38 y su papel en la activación de p38.
- Investigación de los niveles de proteína E-cadherina y la regulación por p38 y p38IP.
Principales resultados:
- La mutación del ojo caído (drey) afecta al empalme de p38IP, lo que lleva a defectos de desarrollo.
- Las mutaciones más fuertes de p38IP causan defectos de gastrulación debido a la migración alterada del mesodermo y la regulación a la baja de la E-cadherina.
- p38IP se une directamente y se requiere para la activación de p38 in vivo.
- Tanto la p38 como la p38IP son necesarias para la regulación a la baja de la E-cadherina durante la gastrulación.
- p38 regula la expresión de la proteína E-cadherina aguas abajo de la quinasa que interactúa con NCK (NIK) e independientemente de la señalización de Fgf y Snail.
Conclusiones:
- p38 MAP quinasa y p38IP son reguladores críticos de la regulación a la baja de la E-cadherina durante la gastrulación de los vertebrados.
- p38IP actúa como un andamio o activador para la señalización de p38 in vivo.
- La interrupción de la vía p38/p38IP conduce a defectos de gastrulación al afectar la migración del mesodermo.
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