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El papel de YAP/TAZ en la mecanotransducción
Sirio Dupont1, Leonardo Morsut, Mariaceleste Aragona
1Department of Histology, Microbiology and Medical Biotechnologies, University of Padua School of Medicine, viale Colombo 3, 35131 Padua, Italy. dupont@bio.unipd.it
Nature
|June 10, 2011
Resumen
Las células perciben su entorno físico a través de señales mecánicas. El estudio identifica las proteínas YAP / TAZ como relés nucleares clave que traducen estas señales mecánicas en respuestas celulares, impactando el comportamiento y la diferenciación celular.
Área de la Ciencia:
- Biología celular Biología celular.
- Mecanobiología Mecanobiología.
- La bioquímica es la bioquímica.
Sus antecedentes:
- Las células responden a señales solubles y señales físicas como la rigidez de la matriz extracelular (ECM).
- La mecanotransducción traduce los estímulos físicos en señales bioquímicas que influyen en el comportamiento celular, el crecimiento, la diferenciación y la progresión del cáncer.
- No se comprende bien el vínculo entre el mecanismo de detección de rigidez y la actividad del factor de transcripción nuclear.
Objetivo del estudio:
- Para identificar los relés nucleares que median las señales mecánicas del microambiente celular.
- Para investigar el papel de las proteínas YAP / TAZ en la detección de la rigidez del ECM y la forma de la célula.
- Comprender cómo las señales mecánicas influyen en la diferenciación celular y las vías de supervivencia.
Principales métodos:
- Identificación de YAP (proteína asociada al sí) y TAZ (coactivador transcripcional con motivo de unión a la PDZ, WWTR1) como proteínas clave.
- Investigación de la actividad de la Rho GTPasa y la tensión del citoesqueleto de la actomyosina.
- Evaluación de la función YAP/TAZ en la diferenciación de las células madre mesenquimales y la supervivencia de las células endoteliales.
- Análisis de la regulación YAP/TAZ independiente de la cascada Hippo/LATS.
Principales resultados:
- YAP y TAZ actúan como relés nucleares para las señales mecánicas de la rigidez ECM y la forma de la célula.
- Esta regulación depende de la actividad de la Rho GTPasa y la tensión de la actomyosina, pero no de la cascada Hippo/LATS.
- YAP/TAZ son esenciales para la diferenciación de células madre mesenquimales inducida por la rigidez de la ECM.
- YAP/TAZ median la supervivencia de las células endoteliales reguladas por la geometría celular.
- El YAP activado puede anular las restricciones físicas para dictar el comportamiento celular.
Conclusiones:
- Las proteínas YAP / TAZ se identifican como sensores críticos y mediadores de señales mecánicas del microambiente celular.
- Estos hallazgos esclarecen una nueva vía que vincula las restricciones físicas celulares con la actividad del factor de transcripción nuclear.
- El estudio destaca la importancia de la mecanotransducción en procesos celulares fundamentales como la diferenciación y la supervivencia.
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