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La AAA+ ATPasa Torasa regula la plasticidad sináptica y el comportamiento dependientes del receptor AMPA
Jianmin Zhang1, Yue Wang, Zhikai Chi
1Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell
|April 19, 2011
Resumen
La AAA+ ATPasa Torasa regula los receptores AMPA de superficie (AMPAR) mediante la mediación de su internalización. La eliminación de Thorase perjudica la eliminación de AMPAR, afectando la plasticidad sináptica y llevando a déficits de aprendizaje y memoria.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- La plasticidad sináptica, incluida la potenciación a largo plazo (LTP) y la depresión a largo plazo (LTD), es crucial para el aprendizaje y la memoria.
- La expresión superficial de los receptores AMPA (AMPAR) es un regulador clave de la actividad sináptica y la plasticidad.
Objetivo del estudio:
- Identificar y caracterizar nuevos reguladores moleculares de la expresión superficial de AMPAR.
- Para aclarar el papel de la AAA+ ATPasa Torasa en la plasticidad sináptica y la función cognitiva.
Principales métodos:
- Caracterización de la función de la torasa en las células neuronales.
- Eliminación genética de la torasa en ratones (Torasa nula).
- Registros electrofisiológicos de corrientes postsinápticas excitatorias en miniatura (mEPSC).
- Evaluación de LTP y LTD en ratones Thorase nulos.
- Pruebas de comportamiento para déficits de aprendizaje y memoria.
Principales resultados:
- La torasa, una ATPasa AAA+, fue identificada como un regulador de la expresión de AMPAR superficial.
- La torasa media la internalización de AMPAR a través del desmontaje dependiente de la ATPasa del complejo AMPAR-GRIP1.
- La eliminación genética de la torasa redujo significativamente la internalización de AMPAR.
- Los ratones Thorase null exhibieron amplitudes mEPSC aumentadas, LTP mejorado y LTD. abolido.
- Los ratones Thorase null mostraron déficits significativos en el aprendizaje y la memoria.
Conclusiones:
- La torasa juega un papel crítico en la regulación de la expresión superficial de AMPAR a través de la internalización del receptor.
- La interrupción de la función de Thorase conduce a una plasticidad sináptica aberrante y a un aprendizaje y memoria alterados.
- La torasa representa un nuevo objetivo molecular para la comprensión y el tratamiento potencial de los trastornos cognitivos.
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