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La regulación del acoplamiento de la proteína G del receptor de serotonina-2C por medio de la edición del ARN

C M Burns¹, H Chu, S M Rueter

¹Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6600, USA.

|May 15, 1997

Resumen

La edición del ARN de los receptores de serotonina 5-HT2C altera su función. Esta modificación post-transcripcional cambia las isoformas de los receptores, afectando la transducción de la señal y las funciones celulares reguladas por los receptores acoplados a la proteína G.

Área de la Ciencia:

La neurociencia es la neurociencia.
Biología Molecular Biología Molecular
Genética La genética.

Sus antecedentes:

La serotonina (5-hidroxitriptamina, 5-HT) media los efectos fisiológicos a través de los subtipos de los receptores.
La familia de receptores 5-HT2, incluido el 5-HT2C, son receptores acoplados a proteínas G vinculados a la fosfolipasa C.
La activación de los receptores 5-HT2 aumenta el fosfato de inositol intracelular y el diacilglicerol.

Objetivo del estudio:

Para investigar los eventos de edición de ARN en las transcripciones de los receptores de serotonina 5-HT2C (5-HT2CR).
Para determinar el impacto de la edición de ARN en la expresión y función de 5-HT2CR.
Para explorar la edición de ARN como un mecanismo regulador para la señalización serotoninérgica.

Principales métodos:

Análisis de secuencia de ADN complementario (ADNc) de regiones disecadas del cerebro.
Identificación y caracterización de los eventos de edición de ARN de 5-HT2CR.
Evaluación de las consecuencias funcionales de la edición de ARN en las interacciones receptor-proteína G.

Principales resultados:

Las transcripciones 5-HT2CR se someten a la edición del ARN, convirtiendo la adenosina en inosina a través de las desaminasas de adenosina.
Se observó la expresión específica del tejido de siete isoformas principales de 5-HT2CR de once especies distintas de ARN.
La edición de ARN altera la secuencia de aminoácidos en el segundo bucle intracelular, reduciendo la eficacia de la interacción receptor-proteína G en 10 a 15 veces.

Conclusiones:

La edición de ARN representa un nuevo mecanismo para regular la transducción de señales serotoninérgicas.
La modificación post-transcripcional de 5-HT2CR a través de la edición de ARN es crítica para la modulación de las funciones celulares.
Este mecanismo puede ser relevante para otros receptores acoplados a la proteína G.

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