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Identificación de la F-actina como el eje dinámico en un circuito de polaridad de GTPasa inducida por microbios
Robert C Orchard1, Mark Kittisopikul, Steven J Altschuler
1Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cell
|February 21, 2012
Resumen
Los patógenos bacterianos secuestran la polaridad celular utilizando un factor de intercambio guanina-nucleótido (GEF) que interactúa con la F-actina. Esta interacción impulsa la polarización de la Cdc42 GTPasa, revelando un mecanismo conservado para la polaridad celular en mamíferos y bacterias.
Área de la Ciencia:
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
- Microbiología Microbiología.
Sus antecedentes:
- La polaridad celular es crucial para la función celular de los mamíferos y está regulada por complejas redes de señalización.
- Los patógenos bacterianos pueden manipular estas vías de la célula huésped para su propio beneficio.
Objetivo del estudio:
- Descubrir los principios fundamentales de la polaridad celular de los mamíferos y la patogénesis bacteriana.
- Para investigar el papel del factor de intercambio enteropatogénico Escherichia coli guanina-nucleótido (GEF) Mapa en la señalización de la GTPasa Cdc42.
Principales métodos:
- Desarrollo de un modelo teórico y experimental tratable.
- Derivados sintéticos usados del Mapa GEF.
- Empleó modelos matemáticos para analizar la dinámica de la actina y los circuitos de retroalimentación.
Principales resultados:
- Se descubrió que la transducción de la señal de Cdc42 GTPasa está controlada por la interacción entre Map GEF y F-actin.
- Se demostró que la dinámica de actina y un bucle de retroalimentación positiva dependiente de Map polarizan espontáneamente Cdc42 en la membrana plasmática.
- Se demostró que recablear el circuito de señalización para estimular la β-integrina permite la polarización de Cdc42 en respuesta a señales extracelulares.
Conclusiones:
- Propuso una vía molecular para la polaridad celular centrada en la interacción entre los GEF y la F-actina.
- Es probable que este mecanismo se conserve y funcione en diversos sistemas biológicos, incluidas las células de mamíferos y las infecciones bacterianas.
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