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La regulación dependiente de la actividad de los factores de transcripción MEF2 suprime el número de sinapsis
Steven W Flavell1, Christopher W Cowan, Tae-Kyung Kim
1Neurobiology Program, Children's Hospital, and Departments of Neurology and Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Science (New York, N.Y.)
|February 18, 2006
Resumen
Los factores de transcripción del factor potenciador de miocitos 2 (MEF2) controlan el número de sinapsis en respuesta a la actividad neuronal. El MEF2 activado restringe la formación de sinapsis excitatorias promoviendo la transcripción génica durante el desarrollo del sistema nervioso.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- Biología del desarrollo Biología del desarrollo.
Sus antecedentes:
- La actividad neuronal es crucial para regular la formación de sinapsis en el sistema nervioso de los mamíferos.
- Los mecanismos genéticos subyacentes que coordinan el desarrollo de las sinapsis no se comprenden completamente.
Objetivo del estudio:
- Investigar el papel de los factores de transcripción del factor 2 potenciador de miocitos (MEF2) en la regulación del número de sinapsis durante el desarrollo neuronal.
- Para dilucidar la vía molecular que vincula la actividad neuronal a la regulación de las sinapsis.
Principales métodos:
- Se utilizaron cultivos de neuronas del hipocampo para estudiar la formación de sinapsis.
- Investigó la regulación dependiente de la actividad del MEF2 por la calcineurina.
- Analizó los objetivos de transcripción de MEF2, incluyendo arc y synGAP.
Principales resultados:
- Se encontró que los factores de transcripción del factor potenciador de miocitos 2 (MEF2) suprimen el número de sinapsis excitatorias de una manera dependiente de la actividad neuronal y la calcineurina.
- El aumento de la actividad neuronal condujo a la afluencia de calcio, activando la calcineurina, que a su vez desfosforilado y activado MEF2.
- El MEF2 activado promovió la transcripción de genes como el arco y el synGAP, que limitan el número de sinapsis.
Conclusiones:
- Se ha definido un programa transcripcional dependiente de la actividad que involucra al MEF2 y que regula el número de sinapsis.
- Esta vía proporciona un mecanismo para controlar la formación de sinapsis durante el desarrollo del sistema nervioso.
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