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La supresión dependiente de la actividad y del mTOR de la traducción del ARNm del canal Kv1.1 en dendritas
Kimberly F Raab-Graham1, Patrick C G Haddick, Yuh Nung Jan
1Howard Hughes Medical Institute, Departments of Physiology and Biochemistry, University of California, San Francisco, CA 94158, USA.
Science (New York, N.Y.)
|October 7, 2006
Resumen
La inhibición de la vía de la meta de la rapamicina (mTOR) en mamíferos aumenta la expresión del canal de potasio Kv1.1 en las dendritas de las neuronas del hipocampo. Esto sugiere que la excitación sináptica puede suprimir los canales Kv1 dendríticos al reducir su síntesis local.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
Sus antecedentes:
- El objetivo mamífero de la vía de la rapamicina (mTOR) regula la plasticidad sináptica y la síntesis de proteínas locales en las dendritas neuronales.
- Kv1.1 Los canales de potasio regulados por voltaje son cruciales para la excitabilidad neuronal y la función sináptica.
Objetivo del estudio:
- Investigar el efecto de la inhibición de mTOR en la expresión y localización del canal Kv1.1 en las neuronas del hipocampo.
- Para determinar si Kv1.1 se sintetiza localmente en las dendritas y si esta síntesis está regulada por la actividad del receptor mTOR o N-metil-d-aspartato (NMDA).
Principales métodos:
- Tratamiento de las neuronas del hipocampo con el inhibidor de mTOR rapamicina.
- Evaluación de los niveles de proteínas Kv1.1 y su expresión superficial mediante técnicas bioquímicas e imágenes.
- Detección del ARNm Kv1.1 endógeno en dendritas.
- Utilizando una proteína de fusión Kv1.1-Kaede para monitorear la síntesis de proteínas locales en las dendritas.
Principales resultados:
- El tratamiento con rapamicina aumentó los niveles totales de proteína Kv1.1 y mejoró la expresión superficial de Kv1.1 específicamente en las dendritas, sin afectar la expresión axonal.
- El ARNm endógeno Kv1.1 se detectó dentro de las dendritas.
- La inhibición de los receptores mTOR o NMDA condujo a la síntesis observable de Kv1.1 en las dendritas.
Conclusiones:
- La señalización mTOR regula negativamente la síntesis local y la expresión de la superficie dendrítica de los canales Kv1.1.
- La excitación sináptica, potencialmente a través de la activación del receptor NMDA, puede suprimir la función del canal Kv1 dendrítico al reducir su síntesis local.
- Estos hallazgos revelan un nuevo mecanismo regulador para los canales Kv1.1 que afectan la plasticidad sináptica y la excitabilidad neuronal.
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