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Especificidad sináptica directa de las GPCR de latrofilina por unión coincidente de las FLRT y las teneurinas
Richard Sando1, Xian Jiang1, Thomas C Südhof2
1Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University Medical School, Stanford, CA 94305, USA.
Science (New York, N.Y.)
|February 23, 2019
Resumen
Las moléculas de adhesión celular guían la formación de sinapsis. La latrofilina-3, un receptor acoplado a la proteína G, requiere la unión a las proteínas transmembrana repetidas ricas en leucina de la fibronectina (FLRT) y las teneurinas para formar sinapsis hipocampal específicas.
Área de la Ciencia:
- La neurociencia
- Biología molecular
- Biología celular
Sus antecedentes:
- Las moléculas de adhesión celular median la señalización bidireccional, crucial para la formación de sinapsis.
- Los mecanismos precisos que subyacen a la especificidad de las sinapsis siguen siendo en gran medida desconocidos.
Objetivo del estudio:
- Aclarar el papel de los receptores acoplados a proteínas G de adhesión (GPCR) en la dirección de la formación de sinapsis específicas en las neuronas del hipocampo.
- Investigar las interacciones moleculares de latrophilin-3 con sus ligandos en el desarrollo de la sinapsis.
Principales métodos:
- Se utilizaron ratones transgénicos para estudios in vivo de la formación de sinapsis.
- Se utilizan cultivos neuronales in vitro para evaluar los efectos funcionales de la unión al ligando.
- Se han investigado las interacciones de unión de la latrophilina-3 con las proteínas transmembrana repetidas ricas en leucina de la fibronectina (FLRT) y las tenurinas.
Principales resultados:
- La latrophilina-2 y la latrophilina-3 dirigen selectivamente la formación de sinapsis perforante y colateral de Schaffer, respectivamente, en las neuronas CA1 del hipocampo.
- La unión de la latrofilina-3 tanto a las FLRT como a las teneurinas es esencial para la formación de sinapsis específicas de entrada in vivo.
- La aplicación conjunta de teneurina y FLRT, pero no individualmente, indujo la formación de sinapsis excitatorias potentemente in vitro.
Conclusiones:
- Las latrophilinas postsinápticas orquestan la formación de sinapsis excitatorias a través de la unión simultánea de ligandos presinápticos distintos.
- Este mecanismo de unión de doble ligando es crítico para establecer entradas sinápticas en ubicaciones dendríticas precisas.
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