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El complejo de clasificación endosómica ESCRT-II media el ensamblaje y la arquitectura de las hélices ESCRT-III
William Mike Henne1, Nicholas J Buchkovich, Yingying Zhao
1Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
Cell
|October 16, 2012
Resumen
Los complejos de clasificación endosómica requeridos para la maquinaria de transporte (ESCRT), en particular el ESCRT-III, impulsan la formación de vesículas. Este estudio visualiza los supercomplejos ESCRT-II:ESCRT-III, revelando cómo esculpen las membranas para los procesos celulares.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología molecular y estructural Biología molecular y estructural.
Sus antecedentes:
- Los complejos de clasificación endosómica requeridos para el transporte (ESCRT) son cruciales para la remodelación de la membrana en procesos como la biogénesis de cuerpos multivesiculares (MVB).
- La estructura y el mecanismo precisos de ESCRT-III en la formación de vesículas siguen siendo en gran medida indefinidos.
Objetivo del estudio:
- Aclarar la estructura y el mecanismo de los supercomplejos ESCRT-II y ESCRT-III en la mediación de eventos de escultura de la membrana.
- Comprender cómo la activación y el ensamblaje de las subunidades de la ESCRT-III conducen a la formación de vesículas.
Principales métodos:
- Se utilizó microscopía electrónica para visualizar el supercomplejo ESCRT-II:ESCRT-III.
- Los ensayos de monocapa de lípidos caracterizaron el ensamblaje de subunidades ESCRT-III.
- La citometría de flujo de alto contenido evaluó el impacto de las mutaciones del ensamblaje ESCRT-III en la función.
Principales resultados:
- La subunidad ESCRT-III Snf7 forma protofilamentos en espiral tras su activación.
- ESCRT-II, Vps24 y Vps2 transforman estas espirales en hélices de escultura de membrana.
- ESCRT-II y ESCRT-III se ensamblan en estructuras en forma de anillo, lo que sugiere el secuestro de carga.
Conclusiones:
- La ESCRT-III pasa por distintas etapas arquitectónicas moduladas por la ESCRT-II.
- El ensamblaje ordenado de ESCRT-III, guiado por ESCRT-II, media la captura de carga y la formación de vesículas.
- Esto proporciona una base estructural para la remodelación de la membrana mediada por ESCRT.
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