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Visualización de los complejos de auto-reconocimiento neuronal de protocadherina agrupados
Julia Brasch1,2,3, Kerry M Goodman1,3, Alex J Noble2
1Zuckerman Mind, Brain and Behavior Institute, Columbia University, New York, NY, USA.
Nature
|April 12, 2019
Resumen
El auto-reconocimiento de las neuritas se basa en protocadherinas agrupadas que forman estructuras parecidas a cremalleras. Estos ensamblajes moleculares median la evitación neuronal, crucial para el desarrollo y la función adecuados del sistema nervioso.
Área de la Ciencia:
- La neurociencia
- Biología molecular
- Biología estructural
Sus antecedentes:
- El auto-reconocimiento y la evitación de neuritas son esenciales para el desarrollo del sistema nervioso, guiando la arborización dendrítica y evitando las auto-conexiones.
- Las protocadherinas agrupadas (PCDH) con sus diversas isoformas proporcionan a las neuronas individuales identidades únicas, mediando el auto-reconocimiento.
- Estudios anteriores caracterizaron las interacciones cis y trans de la protocadherina de forma aislada, pero la estructura completa del ectodominio y su papel en el auto-reconocimiento de la superficie neuronal seguían siendo desconocidos.
Objetivo del estudio:
- Determinar la disposición molecular de los ectodomaines de protocadherina agrupados de longitud completa en los complejos de auto-reconocimiento.
- Para aclarar la base estructural de cómo las protocadherinas median el auto-reconocimiento neuronal y la evitación.
Principales métodos:
- Se utilizó la cristalografía de rayos X para determinar la estructura del ectodominio de protocadherina γB4 agrupado.
- Se empleó la tomografía criolectrónica para visualizar el ensamblaje de ectodominos de protocadherina γB6 agrupados en los liposomas.
Principales resultados:
- La estructura cristalina de la protocadherina γB4 agrupada reveló una celosía parecida a una cremallera formada por interacciones cis y trans alternas.
- La tomografía criolectrónica demostró que los ectodominos de protocadherina γB6 agrupados se ensamblan espontáneamente en matrices lineales en los sitios de contacto de la membrana.
- Estos ensamblajes lineales forman matrices paralelas, creando estructuras bidimensionales más grandes entre las membranas, consistentes con la estructura cristalina.
Conclusiones:
- La formación de conjuntos lineales ordenados por protocadherinas agrupadas es un paso inicial clave en el auto-reconocimiento y la evitación neuronal.
- Estos hallazgos apoyan el modelo de terminación de la cadena de desajuste de isoforma del auto-reconocimiento mediado por protocadherina.
- El estudio proporciona información estructural sobre cómo las protocadherinas establecen límites neuronales y aseguran el cableado adecuado del sistema nervioso.
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