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Distribución subcelular regulada de la subunidad NR1 del receptor NMDA
M D Ehlers1, W G Tingley, R L Huganir
1Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Science (New York, N.Y.)
|September 22, 1995
Resumen
El receptor del N-metil-D-aspartato (NMDA, por sus siglas en inglés)
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
Sus antecedentes:
- Los receptores de N-metil-D-aspartato (NMDA) son cruciales para la transmisión sináptica excitatoria en el cerebro de los mamíferos.
- Comprender los mecanismos precisos de localización de los receptores NMDA es clave para comprender la función sináptica.
- Investigaciones anteriores han indicado la importancia de las subunidades específicas de los receptores en la orientación sináptica.
Objetivo del estudio:
- Investigar los mecanismos moleculares responsables de la localización postsináptica de los receptores NMDA.
- Para identificar dominios específicos de proteínas y factores reguladores involucrados en el tráfico y el anclaje de los receptores NMDA.
Principales métodos:
- Expresión de las variantes de empalme de la subunidad NR1 del receptor NMDA en líneas celulares de fibroblastos.
- Análisis de la localización del receptor utilizando microscopía de inmunofluorescencia.
- Estudios funcionales que involucran la inserción de cintas de exones específicas en los receptores AMPA.
- Investigación de los efectos de la fosforilación de la proteína kinasa C en la localización de los receptores.
Principales resultados:
- Variantes de empalme NR1 del receptor NMDA con la primera cinta de exones COOH-terminal localizada en dominios discretos de la membrana plasmática.
- Las variantes NR1 que carecen de esta cinta de exones exhibieron una distribución intracelular difusa.
- La cinta de exones identificada fue suficiente para conferir la localización a los receptores GluR1 AMPA.
- La fosforilación de la proteína quinasa C interrumpió estos dominios de la membrana ricos en receptores.
Conclusiones:
- Secuencias específicas de aminoácidos dentro de la subunidad NR1 del receptor NMDA dictan su localización en dominios discretos de la membrana.
- El empalme alternativo de la subunidad NR1 regula críticamente su orientación subcelular.
- La fosforilación de proteínas, específicamente por la proteína quinasa C, modula la localización del receptor NMDA.
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