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Un papel para la caseína quinasa 2 en el mecanismo subyacente a la compensación de la temperatura circadiana
Arun Mehra1, Mi Shi, Christopher L Baker
1Department of Genetics, Dartmouth Medical School, Hanover, NH 03755, USA.
Cell
|May 20, 2009
Resumen
La caseína quinasa 2 (CK2) regula la compensación de la temperatura en los relojes circadianos de Neurospora. Las mutaciones en las subunidades de CK2 alteran la compensación del reloj al afectar la fosforilación de la proteína FRECUENCIA (FRQ).
Área de la Ciencia:
- Cronobiología cronobiología.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- La compensación de la temperatura es crucial para los ritmos biológicos robustos.
- Los mecanismos moleculares subyacentes a la compensación de la temperatura del reloj circadiano siguen siendo en gran medida desconocidos.
- Estudios anteriores implicaron varias proteínas en la función del reloj, pero no específicamente en la compensación de temperatura.
Objetivo del estudio:
- Para identificar los reguladores clave de la compensación de la temperatura en el reloj circadiano de Neurospora.
- Para aclarar el papel de la caseína quinasa 2 (CK2) en la compensación de la temperatura del reloj circadiano.
- Investigar el mecanismo por el cual CK2 influye en la compensación de temperatura.
Principales métodos:
- Análisis genético de mutantes de reloj de larga data (crono y período-3).
- Análisis bioquímicos para evaluar la actividad de la caseína quinasa 2 (CK2) y la fosforilación del sustrato.
- Mutagénesis dirigida al sitio de los supuestos sitios de fosforilación de CK2 en la proteína FREQUENCY (FRQ).
Principales resultados:
- Los mutantes crono y período-3 codifican las subunidades beta1 y alfa de CK2, respectivamente.
- Reducir la dosis de la subunidad CK2 altera significativamente la compensación de la temperatura sin afectar la cinética de la enzima (Q10).
- CK2 fosforila directamente a FRQ, y esta interacción está deteriorada en los mutantes de CK2; las mutaciones en fosfositos específicos de FRQ imitan los fenotipos mutantes de CK2.
Conclusiones:
- La caseína quinasa 2 (CK2) es un regulador crítico de la compensación de la temperatura en el reloj circadiano de Neurospora.
- CK2 influye en la compensación de la temperatura a través de la fosforilación directa de la proteína FRQ.
- Comprender el papel de CK2 proporciona información sobre el fenómeno general de la compensación biológica.
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