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Regulación de los receptores NMDA por un complejo de señalización asociado de fosfatasa-cinasa

R S Westphal¹, S J Tavalin, J W Lin

¹Howard Hughes Medical Institute, Vollum Institute, Oregon Health Sciences University, 3181 S.W. Sam Jackson Road, Portland, OR 97201, USA.

Science (New York, N.Y.)

|July 3, 1999

Resumen

Yotiao actúa como una proteína de andamio, vinculando la proteína fosfatasa 1 (PP1) y la proteína quinasa A (PKA) a los receptores de N-metil-D-aspartato (NMDA). Esta interacción regula la actividad del receptor NMDA y la transmisión sináptica.

Área de la Ciencia:

La neurociencia es la neurociencia.
Biología Molecular Biología Molecular
La bioquímica es la bioquímica.

Sus antecedentes:

La actividad del receptor de N-metil-D-aspartato (NMDA) está modulada por las quinasas y las fosfatasas, lo que influye en la transmisión sináptica.
Dirigirse a estas enzimas cerca de sus sustratos puede mejorar la modulación dependiente de la fosforilación.

Objetivo del estudio:

Para investigar el papel de la proteína asociada al receptor NMDA, yotiao, en la regulación de la actividad del receptor NMDA.
Para determinar si el yotiao ancla la proteína fosfatasa 1 (PP1) y la proteína quinasa A (PKA) a los receptores NMDA.

Principales métodos:

Los ensayos de coinmunoprecipitación detectan las interacciones de las proteínas.
Grabaciones electrofisiológicas para medir las corrientes del receptor NMDA.

Principales resultados:

Se encontró que Yotiao se une tanto a PP1 como a la holoenzima PKA.
La actividad anclada del PP1 limitó la actividad del canal del receptor NMDA.
La activación de PKA revirtió la actividad de PP1, lo que condujo a un aumento de las corrientes de los receptores NMDA.

Conclusiones:

Yotiao funciona como una proteína de andamio, vinculando físicamente PP1 y PKA a los receptores NMDA.
Este andamiaje regula la actividad del canal del receptor NMDA y la transmisión sináptica.

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