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Las protocadherinas median la autoevitación dendrítica en el sistema nervioso de los mamíferos

Julie L Lefebvre¹, Dimitar Kostadinov, Weisheng V Chen

¹Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.

|July 31, 2012

Resumen

Las protocadherinas agrupadas (Pcdhs) permiten a las neuronas evitar la auto ramificación y distinguir entre células propias y no propias. Esto asegura la formación y el funcionamiento adecuados de los circuitos neuronales.

Área de la Ciencia:

La neurociencia es la neurociencia.
Biología del desarrollo Biología del desarrollo.
Biología Molecular Biología Molecular

Sus antecedentes:

Las arborizaciones dendríticas neuronales tienen el patrón de autoevitación, donde las ramas de la misma neurona se repelen entre sí.
La autoevitación asegura una cobertura completa del territorio de una neurona, minimizando las brechas y las superposiciones.
Algunas neuronas que exhiben autoevitación pueden interactuar con otras neuronas del mismo subtipo, lo que sugiere una discriminación auto/no auto.

Objetivo del estudio:

Investigar el papel de las protocadherinas agrupadas (Pcdhs) en la autoevitación dendrítica y la discriminación de sí mismo/no-sí mismo.
Para dilucidar los mecanismos moleculares por los cuales los Pcdhs regulan el cableado neuronal.

Principales métodos:

Análisis genético de los genes agrupados de protocadherina gamma (Pcdhg) en las células amacrinas de estallido de estrellas (SAC) de la retina del ratón y las células Purkinje cerebelares.
Estudios funcionales que involucran la deleción de genes y el reemplazo de isoformas para evaluar el impacto en la autoevitación dendrítica.
Investigación de las funciones celulares autónomas de las proteínas Pcdhg durante el desarrollo neuronal.

Principales resultados:

La eliminación de los genes Pcdhg interrumpió la autoevitación dendrítica en las células SAC y Purkinje.
Las proteínas Pcdhg actúan de forma celular autónoma; la sustitución de 22 proteínas Pcdhg por una sola isoforma restableció la autoevitación.
La expresión de una sola isoforma de Pcdhg en todos los SACs redujo las interacciones entre las dendritas de los SACs vecinos (interacciones heteroneuronales).

Conclusiones:

Las interacciones homofílicas Pcdhg entre neuritas hermanas (interacciones isoneuronales) generan señales repulsivas, lo que lleva a la autoevitación dendrítica.
La discriminación auto/no auto se logra porque las interacciones heteroneuronales están permitidas a menos que las dendritas compartan un conjunto coincidente de proteínas Pcdhg.
Los vertebrados Pcdhs y los insectos Dscam1 emplean estrategias similares para la autoevitación neuronal y la discriminación de uno mismo/no uno mismo, a pesar de carecer de homología de secuencia.

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