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La forma de la célula y los enlaces negativos en los motivos regulatorios controlan juntos el flujo de información
Susana R Neves1, Panayiotis Tsokas, Anamika Sarkar
1Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1215, New York, NY 10029, USA.
Cell
|May 20, 2008
Resumen
La geometría celular y los bucles de retroalimentación reguladores controlan la propagación de la señal intracelular. Los reguladores negativos, como las fosfatasas, dictan el tamaño del microdominio y la transferencia de información dentro de las neuronas.
Área de la Ciencia:
- Biología celular Biología celular.
- La biofísica es la biofísica.
- La neurociencia computacional es una neurociencia computacional.
Sus antecedentes:
- Las dinámicas espaciales de las redes de señalización intracelular son cruciales para la función celular, pero siguen siendo poco conocidas.
- No está claro cómo el tamaño y la forma de la célula influyen en el origen y la propagación de la información espacial en las vías de señalización.
Objetivo del estudio:
- Para modelar e investigar el papel de la geometría celular en el control de la propagación de la señal intracelular.
- Aclarar el mecanismo por el cual los reguladores negativos y las tasas de reacción influyen en la transferencia de información espacial y las características de señalización de microdominio.
Principales métodos:
- Utilizó ecuaciones diferenciales parciales para modelar el flujo de información espacial en la red de señalización cAMP/PKA/B-Raf/MAPK1,2.
- Incorporó geometrías neuronales reales en simulaciones numéricas.
- Las predicciones del modelo experimentalmente validadas en rebanadas de hipocampo de rata.
Principales resultados:
- Se descubrió que la forma celular rige la dinámica de los reguladores negativos (por ejemplo, fosfodiesterasas, proteínas fosfatasas) dentro de los circuitos reguladores.
- Estos reguladores determinan el tamaño de los microdominios que contienen componentes de señalización activados.
- Las predicciones del modelo con respecto al control del flujo de información espacial por reguladores negativos se confirmaron experimentalmente.
Conclusiones:
- La geometría celular, los bucles de retroalimentación negativa y la cinética de reacción regulan colectivamente la transferencia de información espacial dentro de las células.
- Esto proporciona un mecanismo para cómo las células controlan las características de señalización de microdominio a través de propiedades físicas y bioquímicas.
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