Inducción de espinas dendríticas por un dominio extracelular de la subunidad GluR2 del receptor AMPA
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A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
Maria Passafaro1, Terunaga Nakagawa, Carlo Sala
1DTI Dulbecco Telethon Institute, Cellular and Molecular Pharmacology, Department of Pharmacology, University of Milan, 20129 Italy. m.passafaro@in.cnr.it
Nature
|August 9, 2003
Resumen
El dominio N-terminal del receptor de glutamato 2 (GluR2) en los receptores de ácido propiónico alfa-amino-3-hidroxi-5-metil-4-isoxazol (AMPA) impulsa el crecimiento y la formación de la columna dendrítica en las neuronas, revelando un nuevo mecanismo para la plasticidad sináptica.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- La plasticidad sináptica.
Sus antecedentes:
- Los receptores de glutamato del tipo ácido propiónico alfa-amino-3-hidroxi-5-metil-4-isoxazol (AMPA) median la transmisión sináptica excitatoria en el cerebro de los mamíferos.
- La abundancia de los receptores postsinápticos de AMPA se correlaciona con el tamaño de la sinapsis y las dimensiones de la cabeza de la columna vertebral dendrítica.
- La potenciación a largo plazo implica la formación de la columna vertebral dendrítica y la administración del receptor AMPA, pero los mecanismos subyacentes no están claros.
Objetivo del estudio:
- Investigar los mecanismos moleculares que coordinan la administración del receptor AMPA y la morfogénesis de la columna dendrítica.
- Para determinar el papel de la subunidad del receptor de glutamato 2 (GluR2) en el desarrollo de la columna vertebral.
Principales métodos:
- Sobreexpresión de la subunidad del receptor de glutamato 2 (GluR2) en las neuronas del hipocampo.
- Inducción de la formación de la columna vertebral en las interneuronas que liberan GABA.
- Análisis del papel del dominio extracelular N-terminal (NTD) de GluR2 utilizando proteínas de fusión heterólogas.
Principales resultados:
- La sobreexpresión de GluR2 aumentó el tamaño y la densidad de la columna vertebral en las neuronas del hipocampo.
- Formación de columna inducida por GluR2 en interneuronas GABAérgicas normalmente sin columna vertebral.
- El NTD de GluR2 fue identificado como el dominio clave responsable de la morfogénesis de la columna vertebral, con proteínas de fusión que inhiben el proceso.
Conclusiones:
- El NTD de GluR2 juega un papel crítico en la regulación del crecimiento y / o estabilidad de la columna dendrítica.
- Se propone una interacción receptor-ligando de la superficie celular que involucra el NTD de GluR2 como un mecanismo para la morfogénesis de la columna vertebral.
- Este hallazgo ofrece nuevos conocimientos sobre la base molecular de la plasticidad sináptica y la estructura neuronal.
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