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Regulación de distintos sitios de fosforilación de los receptores AMPA durante la plasticidad sináptica bidireccional
H K Lee1, M Barbarosie, K Kameyama
1Howard Hughes Medical Institute, Department of Neuroscience, Johns Hopkins Medical School, Baltimore, Maryland, USA.
Nature
|July 6, 2000
Resumen
La plasticidad sináptica, al igual que la potenciación a largo plazo (LTP) y la depresión (LTD), implica la fosforilación del receptor AMPA. Estos procesos modifican sitios distintos en la subunidad GluR1, dependiendo de la actividad sináptica previa, revelando vías de señalización dependientes de la historia.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- La plasticidad sináptica.
Sus antecedentes:
- Los cambios en la eficacia de la transmisión sináptica neuronal, incluida la potenciación hipocampal a largo plazo (LTP) y la depresión a largo plazo (LTD), son cruciales para el almacenamiento de información cerebral.
- Se supone que la modulación de la fosforilación del receptor AMPA (ácido propiónico alfa-amino-3-hidroxi-5-metil-4-isoxazloe) puede mediar la LTP y la LTD.
Objetivo del estudio:
- Investigar el papel de la fosforilación de la subunidad GluR1 del receptor AMPA en LTP y LTD.
- Para determinar si LTP y LTD implican la modulación inversa de los mismos sitios de fosforilación o sitios distintos.
- Explorar la influencia de la historia sináptica en las vías de señalización activadas durante LTP y LTD.
Principales métodos:
- Se estudiaron modificaciones reversibles en la fosforilación de la subunidad GluR1 del receptor AMPA durante LTP y LTD.
- Se examinó la especificidad del sitio de fosforilación asociada con la inducción LTP y LTD.
- Investigó el impacto de la potenciación sináptica previa o la depresión en la posterior inducción de la plasticidad.
- Evaluó la sensibilidad diferencial de la LTP a los inhibidores de CaMKII y PKA basado en la historia sináptica.
Principales resultados:
- LTP y LTD alteran reversiblemente la fosforilación de la subunidad GluR1 del receptor AMPA.
- LTP y LTD modulan distintos sitios de fosforilación de GluR1, no sitios inversos.
- La historia sináptica dicta qué sitios de fosforilación están modulados: LTD desfosforila el sitio PKA en sinapsis ingenuas y el sitio CaMKII en sinapsis potenciadas.
- La LTP induce la fosforilación del sitio CaMKII en las sinapsis ingenuas y el sitio PKA en las sinapsis deprimidas.
- La sensibilidad de la LTP a los inhibidores de CaMKII y PKA varía con la historia sináptica.
Conclusiones:
- La fosforilación del receptor AMPA es esencial para la plasticidad sináptica.
- Los mecanismos de plasticidad sináptica no son simples inversos; involucran distintos sitios de fosforilación.
- Las vías de transducción de señales reclutadas por condiciones de estimulación idénticas dependen del historial de actividad previa de la sinapsis.
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