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Los cambios impulsados por la luz en el metabolismo energético activan directamente el oscilador circadiano
Michael J Rust1, Susan S Golden, Erin K O'Shea
1Howard Hughes Medical Institute, Center for Systems Biology, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Science (New York, N.Y.)
|January 15, 2011
Resumen
Los relojes circadianos de las cianobacterias son arrastrados por señales de luz a través de cambios en los niveles de trifosfato de adenosina (ATP) y difosfato de adenosina (ADP). ADP inhibe la actividad de la quinasa, proporcionando una explicación cuantitativa para el arrastre del reloj circadiano.
Área de la Ciencia:
- Mecanismos moleculares de los osciladores biológicos
- Los ritmos circadianos en los procariotas
- Regulación bioquímica de los procesos celulares.
Sus antecedentes:
- Los relojes circadianos exhiben oscilaciones autosuficientes y responden a las señales ambientales.
- La base molecular del arrastre del reloj circadiano no se entiende completamente.
- Las cianobacterias poseen relojes circadianos que son sensibles a la luz.
Objetivo del estudio:
- Para dilucidar los mecanismos moleculares que subyacen en el arrastre del reloj circadiano en las cianobacterias.
- Investigar el papel del trifosfato de adenosina (ATP) y el difosfato de adenosina (ADP) en la regulación del ritmo circadiano.
- Para determinar si los cambios en la proporción de nucleótidos pueden explicar los cambios de fase in vivo.
Principales métodos:
- Reconstrucción in vitro de las oscilaciones circadianas utilizando tres proteínas cianobacterianas y ATP.
- Monitoreo de cambios en las relaciones ATP/ADP en respuesta a cambios de luz en cianobacterias cultivadas.
- Simulación de los cambios de nucleótidos observados en el modelo de oscilador in vitro.
- Desarrollar un modelo matemático limitado por los datos experimentales.
Principales resultados:
- Un oscilador in vitro reconstituido demostró oscilaciones en la fosforilación.
- Los cambios de fase inducidos por la luz in vivo se correlacionan con proporciones alteradas de ATP/ADP.
- Simulando estos cambios de ATP/ADP en el sistema in vitro se replicaron cambios de fase in vivo.
- Se encontró que el difosfato de adenosina (ADP) inhibe la actividad de la quinasa en el oscilador.
Conclusiones:
- Los cambios en la relación ATP / ADP son un mecanismo clave para el arrastre del reloj circadiano en las cianobacterias.
- El difosfato de adenosina (ADP) actúa como un inhibidor directo de la actividad de la quinasa dentro del oscilador circadiano.
- El mecanismo molecular descrito explica cuantitativamente el arrastre del reloj circadiano cianobacteriano por la luz.
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