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Mecanismos moleculares y celulares de la señalización de la teneurina en el emparejamiento sináptico

Chuanyun Xu¹, Zhuoran Li¹, Cheng Lyu²

¹Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; Biology Graduate Program, Stanford University, Stanford, CA 94305, USA.

|July 12, 2024

Resumen

Las teneurinas guían el desarrollo de las conexiones cerebrales mediante la regulación de la señalización de RhoGAP y Rac1. Esta vía estabiliza las ramas de los axones, asegurando la coincidencia precisa de los compañeros sinápticos en las neuronas.

Área de la Ciencia:

La neurociencia
Biología celular
Biología del desarrollo

Sus antecedentes:

La orientación axonal y el emparejamiento sináptico son cruciales para el desarrollo del cerebro.
Las teneurinas son proteínas transmembranales conservadas involucradas en la conectividad sináptica.
Los mecanismos intracelulares por los cuales las teneurinas median el emparejamiento de parejas siguen siendo en gran medida desconocidos.

Objetivo del estudio:

Elucidar las vías de señalización intracelular y los mecanismos celulares subyacentes a la correspondencia sináptica mediada por teneurinas.
Para identificar el interactoma de la teneurina (Ten-m) en el cerebro de Drosophila.
Investigar el papel de la señalización Ten-m en la estabilización de las ramas de los axones y la selección de la pareja.

Principales métodos:

Etiquetado de proximidad in situ para identificar el interactoma intracelular de Ten-m.
Ensayos cuantitativos de coincidencia de parejas en las neuronas receptoras olfativas (ORN) y las neuronas de proyección (PN) de Drosophila.
Análisis del desarrollo en alta resolución de axones individuales y estudios de interacción genética.

Principales resultados:

Se identificó una vía conservada donde Ten-m se une y regula negativamente un RhoGAP, activando las pequeñas GTPasas Rac1.
Se demostró que la señalización Ten-m promueve la acumulación local de F-actina y estabiliza las ramas de los axones ORN.
Se demostró que esta estabilización es crítica para ponerse en contacto con las dendritas PN apropiadas para la correspondencia de parejas sinápticas.

Conclusiones:

Ten-m utiliza una cascada de señalización RhoGAP-Rac1 para regular la dinámica de la F-actina para una coincidencia sináptica precisa.
Este estudio revela los mecanismos moleculares y celulares que rigen la orientación del axón mediada por la teneurina y la formación de sinapsis.
Los hallazgos proporcionan información sobre los procesos fundamentales del desarrollo de circuitos neuronales.

Palabras clave:

Las Drosophila Las GTPasas Rho Se ha comprobado que:Estabilización de las ramas atracción homofílica circuito olfativo neuronas de los receptores olfativos neuronas de proyección Comparación de las parejas sinápticas La tenurina

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