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Cdc42 regula GSK-3beta y la poliposis coli adenomatosa para controlar la polaridad celular
Sandrine Etienne-Manneville1, Alan Hall
1MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, Cancer Research UK Oncogene and Signal Transduction Group, and Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.
Nature
|March 1, 2003
Resumen
La pequeña GTPasa Cdc42 regula la polaridad celular mediante el control de la kinasa-3beta de la sintetasa de glucógeno (GSK-3beta) y la localización de la poliposis coli adenomatosa (Apc) en la célula.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología molecular La biología molecular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La polaridad celular es crucial para la función celular eucariota, incluida la morfogénesis y la migración.
- Se sabe que el complejo Cdc42-Par6-aPKC establece la asimetría celular, pero los efectores aguas abajo no están claros.
Objetivo del estudio:
- Investigar los objetivos posteriores del complejo Par6-aPKC en la migración celular.
- Para dilucidar los mecanismos moleculares por los cuales Cdc42 regula la polaridad celular.
Principales métodos:
- Los astrocitos primarios de rata se utilizaron en ensayos de migración celular.
- Se analizaron las interacciones entre Par6-PKCzeta, GSK-3beta y Apc.
- Se examinó la dinámica de los microtúbulos y la localización de proteínas en el borde principal.
Principales resultados:
- Par6-PKCzeta interactúa directamente con GSK-3beta. y lo regula.
- La fosforilación GSK-3beta dependiente de Cdc42 en el borde principal promueve la polarización del centrosoma.
- GSK-3beta regula la interacción de Apc con los extremos de los microtúbulos más, esencial para la polarización celular.
Conclusiones:
- Cdc42 controla la polaridad celular a través de la regulación espacial de GSK-3beta y Apc.
- El papel de Apc en la asociación de microtúbulos es crítico para la polarización celular.
- Esta vía puede contribuir a las funciones supresoras de tumores de Apc.
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