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Rab5 es necesario para la biogénesis del sistema endolisosomal in vivo

Anja Zeigerer¹, Jerome Gilleron, Roman L Bogorad

¹Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.

|May 25, 2012

Resumen

Las células mantienen la organización endosómica a través de Rab5 (Ras-relacionado en la proteína 5 del cerebro), un regulador clave. El sistema endocítrico muestra resiliencia, colapsando solo cuando los niveles de Rab5 caen críticamente, lo que afecta el número y la función del endosoma.

Área de la Ciencia:

Biología celular Biología celular.
Biología Molecular Biología Molecular
La bioquímica es la bioquímica.

Sus antecedentes:

La regulación del número y el tamaño de los organelos de la membrana es una cuestión fundamental en la biología celular.
Se supone que la pequeña GTPasa Rab5 es un regulador maestro de la biogénesis endosómica.
Comprender el papel de Rab5 es crucial para descifrar el control de la vía endocítica.

Objetivo del estudio:

Investigar el papel de Rab5 en la biogénesis del endosoma y su organización in vivo.
Para determinar los niveles críticos de Rab5 requeridos para la función del sistema endocítrico.
Para aclarar los mecanismos de resiliencia del sistema endocítrico.

Principales métodos:

Desarrollo de un modelo matemático para la dependencia endosómica en Rab5.
Validación in vivo utilizando interferencia de ARN para agotar las isoformas de Rab5 en el hígado de ratón adulto.
Análisis del número de endosomas, tamaño y tráfico de carga en el agotamiento de Rab5.

Principales resultados:

El sistema endocítrico exhibió una resistencia inesperada al agotamiento de Rab5.
El colapso del endosoma ocurrió solo cuando los niveles de Rab5 disminuyeron por debajo de un umbral crítico.
La pérdida de Rab5 condujo a un número reducido de endosomas tempranos, endosomas tardíos y lisosomas, bloqueando la endocitosis LDL.
El fracaso en la entrega de proteínas apical a los canaliculi biliares indicó un papel en la clasificación polarizada de la carga.

Conclusiones:

Rab5 funciona como un organizador crítico in vivo de los endosomas.
El sistema endocítrico posee importantes mecanismos de resiliencia.
Los niveles de Rab5 son esenciales para mantener la homeostasis endosómica y el transporte de proteínas polarizadas.

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