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La coordinación de las actividades de kinasa y fosfatasa por Lem4 permite el reensamblaje de la envoltura nuclear
Claudio Asencio1, Iain F Davidson, Rachel Santarella-Mellwig
1European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Cell
|July 10, 2012
Resumen
La reformación de la envoltura nuclear requiere la desfosforilación de la proteína BAF. La proteína conservada Lem4 / LEM-4L regula este proceso inhibiendo una quinasa e interactuando con una fosfatasa, asegurando la división celular adecuada.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- El desmontaje y el reensamblaje de la envoltura nuclear (NE) son eventos críticos durante la mitosis en los metazoos.
- La fosforilación mitótica de la proteína BAF (factor de barrera a la autointegración) interrumpe su interacción con la cromatina y las proteínas de la membrana nuclear interna, facilitando el desmontaje de la NE.
- La regulación precisa de la desfosforilación de BAF durante la salida mitótica, esencial para el reensamblaje de NE, sigue siendo en gran medida desconocida.
Objetivo del estudio:
- Investigar los mecanismos reguladores que controlan la desfosforilación de BAF durante la salida mitótica.
- Identificar las proteínas involucradas en la desfosforilación del BAF y la posterior reformación de la envoltura nuclear.
- Para dilucidar la función conservada de Lem4/LEM-4L en la dinámica de la envolvente nuclear.
Principales métodos:
- Utilizó el organismo modelo C. elegans y líneas celulares humanas.
- Investigó el papel de LEM-4L y su ortólogo humano Lem4 (ANKLE2) en la desfosforilación de BAF.
- Se realizaron experimentos in vivo e in vitro para analizar la interacción de Lem4/LEM-4L con las quinasas (VRK-1) y las fosfatasas (PP2A).
Principales resultados:
- LEM-4L y Lem4 son esenciales para la desfosforilación de BAF durante la salida mitótica.
- Lem4/LEM-4L inhibe la actividad de la kinasa mitótica VRK-1 hacia BAF.
- Lem4/LEM-4L interactúa con la fosfatasa PP2A y es necesaria para que ésta desfosforile BAF.
- Esta regulación coordinada por Lem4/LEM-4L asegura la formación adecuada de la envoltura nuclear postmitótica.
Conclusiones:
- Lem4/LEM-4L actúa como un regulador crucial de la desfosforilación de BAF, integrando las señales de ambas vías de la quinasa y la fosfatasa.
- La función de Lem4/LEM-4L en el control del reensamblaje de la envoltura nuclear se conserva en todas las especies, desde C. elegans hasta los humanos.
- Comprender el papel de Lem4/LEM-4L proporciona información sobre los procesos fundamentales de la división celular y la dinámica de la envoltura nuclear.
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