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Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells
Published on: February 18, 2014
Dissección de la degradación asociada a ER de una proteína de membrana politópica mal plegada
Kunio Nakatsukasa1, Gregory Huyer, Susan Michaelis
1Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Cell
|January 15, 2008
Resumen
Las chaperonas ayudan activamente a degradar las proteínas de membrana mal plegadas a través de la degradación asociada al retículo endoplasmático (ERAD). La poliubiquitinación y el complejo Cdc48 son cruciales para extraer estas proteínas de la ER para su destrucción.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- La degradación de las proteínas.
Sus antecedentes:
- La degradación de las proteínas de membrana mal plegadas a través de ERAD no se entiende completamente.
- Las chaperonas pueden solubilizar motivos propensos a la agregación.
- ERAD de proteínas de membrana es complejo y requiere una mayor aclaración.
Objetivo del estudio:
- Reconstituir y definir la vía ERAD para la proteína politópica de la membrana Ste6p.
- Para aclarar las funciones de las chaperonas y las ligasas de la ubiquitina en la proteína de membrana ERAD.
- Para investigar el mecanismo de extracción y degradación de proteínas de membrana.
Principales métodos:
- Reconstitución de la vía de ERAD del paso 6 in vitro.
- Análisis de la participación del chaperón antes de la ubiquitinación.
- Investigación de las funciones del complejo Cdc48 y Ufd2p en la retrotranslocación y degradación.
Principales resultados:
- Las chaperonas específicas de Hsp70/40 facilitan la asociación de Ste6p con las ligasas E3.
- Se requiere poliubiquitinación para la retrotranslocación, que involucra el complejo Cdc48 y ATP.
- La extracción de paso 6 fue soluble e independiente de Ufd2p, pero Ufd2p aumentó la ubiquitinación y la degradación.
Conclusiones:
- Las proteínas de membrana politópica se pueden extraer de la ER durante el ERAD.
- Las chaperonas juegan un papel activo en la orientación de proteínas de membrana mal plegadas para la degradación.
- Ufd2p influye en el grado de ubiquitinación y la velocidad de degradación de las proteínas de la membrana.
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