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Las proteínas RIM atan los canales de Ca2+ a las zonas activas presinápticas a través de una interacción directa

Pascal S Kaeser¹, Lunbin Deng, Yun Wang

¹Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305-5453, USA.

|January 19, 2011

Resumen

La proteína de la zona activa RIM se une directamente a los canales de calcio, cruciales para la liberación de las vesículas sinápticas. Esta interacción ata los canales de calcio a las zonas activas, lo que permite la liberación rápida de neurotransmisores.

Área de la Ciencia:

La neurociencia es la neurociencia.
Biología Molecular Biología Molecular
La plasticidad sináptica.

Sus antecedentes:

La liberación rápida y sincrónica de neurotransmisores en las sinapsis depende de la localización del canal Ca2+ en las zonas activas presinápticas.
El mecanismo de reclutamiento de los canales de Ca2+ a estas zonas activas sigue siendo poco conocido.

Objetivo del estudio:

Identificar los mecanismos moleculares subyacentes al reclutamiento de canales Ca2+ en las zonas activas presinápticas.
Para aclarar el papel de la proteína de la zona activa RIM en este proceso.

Principales métodos:

Las pantallas de dos híbridos de levadura imparcial para identificar las interacciones de proteínas.
Generación y análisis de ratones con knockout condicional que carecen de las isoformas RIM.
Experimentos de rescate funcional utilizando dominios específicos de proteínas.

Principales resultados:

Se identificó una interacción directa entre el dominio PDZ de RIM y los terminales C de los canales N- y P/Q de tipo Ca2+.
La eliminación de las proteínas RIM alteró la localización del canal Ca2+ y el primado de las vesículas sinápticas, lo que abolió la liberación de neurotransmisores.
Los experimentos de rescate mostraron que el dominio RIM PDZ es esencial para la localización del canal Ca2+, mientras que el extremo N es crucial para la preparación de las vesículas.

Conclusiones:

Las proteínas RIM se unen directamente a los canales Ca2+ de tipo N y P/Q a las zonas activas presinápticas a través de una interacción mediada por el dominio PDZ.
Esta interacción es crítica para permitir la liberación rápida y sincrónica de neurotransmisores en las sinapsis.

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