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La separación de fases de LEM2 promueve la reforma de la envolvente nuclear mediada por el ESCRT

Alexander von Appen¹, Dollie LaJoie², Isabel E Johnson¹

¹Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.

|June 5, 2020

Resumen

La reformación de la envoltura nuclear se basa en la condensación de la proteína LEM2 en los microtúbulos del huso, activando los complejos ESCRT para el sellado nuclear y la división celular adecuada. Este proceso es crucial para mantener la integridad nuclear y prevenir el daño del ADN.

Área de la Ciencia:

Biología celular
Biología molecular
Dinámica de la cromatina

Sus antecedentes:

La remodelación de la envoltura nuclear (NE) es esencial para la segregación cromosómica durante la división celular.
La reformación de núcleos sellados después de la mitosis requiere complejos de clasificación endosómica necesarios para el transporte (ESCRT) y el adaptador ESCRT transmembrana LEM2.

Objetivo del estudio:

Aclarar el mecanismo por el cual la condensación LEM2 en los microtúbulos regula la activación de la ESCRT y el desmontaje del husillo.
Investigar el papel de los distintos dominios de LEM2 en la unión de la cromatina, la separación de fases y la interacción de los microtúbulos.

Principales métodos:

Se investigó la interacción de LEM2 con BAF, cromatina y microtúbulos utilizando ensayos bioquímicos.
Se analizaron las propiedades de separación de fase de LEM2 y su orientación a los microtúbulos del husillo.
Se examinó la activación de la proteína híbrida ESCRT-II/ESCRT-III CHMP7 por el dominio de hélice alada de LEM2.
Eventos interrumpidos mediados por LEM2 en células humanas para evaluar las consecuencias funcionales.

Principales resultados:

El motivo LEM2 de LEM se une a BAF para la asociación de cromatina, mientras que su dominio de baja complejidad (LCD) media la separación de fase y la unión de microtúbulos.
LEM2 se condensa en los microtúbulos del huso, activando el CHMP7 para formar anillos co-oligoméricos.
La interrupción de la función LEM2 en las células humanas afectó el reclutamiento de ESCRT, el desmontaje del huso y condujo a defectos nucleares y daños en el ADN.

Conclusiones:

LEM2 se somete a la separación de la fase líquida y co-ensambla con CHMP7 para formar un "sello de anillo O" crucial en la interfaz membrana-cromatina-huso durante el reensamblaje nuclear.
Este mecanismo destaca el papel de la separación de fases en la coordinación de la reformación de la envoltura nuclear y el desmontaje del husillo.
Los hallazgos sugieren que la separación de fases contribuye a otras funciones de la envoltura nuclear, incluida la reparación interfásica y la organización de la cromatina.

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