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El receptor humano de serotonina 5-HT ((1A) se segrega preferentemente a la fase desordenada líquida en las bicapas

M Gertrude Gutierrez¹, Noah Malmstadt

¹Mork Family Department of Chemical Engineering and Materials Science, University of Southern California , 925 Bloom Walk, Los Angeles, California 90089, United States.

Journal of the American Chemical Society

|September 12, 2014

Resumen

Las vesículas unilamellares gigantes incorporaron con éxito el receptor de serotonina 1A (5-HT1A). Este receptor acoplado a la proteína G prefiere las regiones de la membrana pobres en colesterol, desafiando las teorías anteriores de la balsa de lípidos.

Área de la Ciencia:

La bioquímica es la bioquímica.
Biofísica de las membranas Biofísica de las membranas.
Farmacología Farmacología.

Sus antecedentes:

Los receptores acoplados a la proteína G (GPCR) son objetivos farmacológicos cruciales.
Comprender la localización de la membrana de los GPCR es clave para su función.
Estudios anteriores sugirieron que los receptores 5-HT1A se asocian con las balsas de lípidos.

Objetivo del estudio:

Para incorporar el receptor 5-HT1A en las vesículas unilamelares gigantes (VUG).
Para investigar la preferencia de fase de membrana del receptor 5-HT1A.
Para determinar la influencia del colesterol y la esfingomielina en la localización del 5-HT1A.

Principales métodos:

Utilizó un método de rehidratación de agarosa para la formación de GUV.
Incorporó el receptor 5-HT1A en las GUV.
Empleado microscopía de fluorescencia para la observación directa de la localización del receptor.

Principales resultados:

Se ha demostrado con éxito la incorporación de 5-HT1A en GUVs.
Se observó segregación preferencial de 5-HT1A en la fase líquida desordenada.
Se encontró que las concentraciones de colesterol y esfingomielina no afectaron la segregación de 5-HT1A en la fase líquida desordenada, lo que contradice la asociación de la balsa de lípidos.
Se observó directamente la localización de 5-HT1A utilizando técnicas de fluorescencia.

Conclusiones:

El receptor 5-HT1A se localiza en los dominios de la membrana del líquido desordenado pobre en colesterol.
Este hallazgo desafía el modelo establecido de asociación de los receptores 5-HT1A con las balsas de lípidos.
La composición lipídica de la membrana, específicamente el colesterol y la esfingomielina, no dicta la segregación de fase preferente de 5-HT1A.

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