La activación de la caspasa-3 a través de las mitocondrias es necesaria para la depresión a largo plazo y la
Zheng Li1, Jihoon Jo, Jie-Min Jia
1The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. lizheng2@mail.nih.gov
Cell
|June 1, 2010
Resumen
La activación de la caspasa-3 mitocondrial es crucial para la depresión a largo plazo (LTD) y la eliminación del receptor AMPA en las neuronas. Esta vía de apoptosis es esencial para la plasticidad sináptica sin causar la muerte celular.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
Sus antecedentes:
- La plasticidad sináptica, incluida la depresión a largo plazo (LTD), es vital para la función cerebral.
- LTD implica la eliminación del receptor AMPA, pero sus impulsores moleculares no se comprenden completamente.
Objetivo del estudio:
- Investigar los mecanismos moleculares subyacentes a la internalización del receptor AMPA durante el LTD.
- Para determinar el papel de las proteínas relacionadas con la apoptosis en la plasticidad sináptica.
Principales métodos:
- Utilizó inhibidores péptidos de la caspasa-3 y -9.
- Se generó y estudió caspase-3 knockout ratones.
- Proteínas anti-apoptóticas sobre expresadas (XIAP, Bcl-xL) y una proteína mutante Akt1.
- Examinó la estimulación del receptor NMDA en las neuronas y las rebanadas del hipocampo.
Principales resultados:
- La activación de la caspasa-3, iniciada por las mitocondrias, es necesaria para la internalización de los receptores LTD y AMPA.
- La inhibición de la caspasa-3 o -9 bloqueó la LTD y la eliminación del receptor.
- LTD fue abolida en ratones caspase-3 knockout, mientras que LTP no se vio afectado.
- La sobreexpresión de XIAP, Bcl-xL, o un Akt1 resistente a la caspasa impidió que LTD.
- La estimulación del receptor NMDA activó la caspasa-3 en las dendritas sin inducir la apoptosis.
Conclusiones:
- La activación mitocondrial de la caspasa-3 es un mecanismo molecular clave que impulsa el LTD.
- La maquinaria molecular de la vía apoptótica está inesperadamente involucrada en la plasticidad sináptica.
- La caspasa-3 juega un papel crítico en la regulación del tráfico de receptores AMPA durante la LTD.
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