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Olfaction

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Perforated Patch-clamp Recording of Mouse Olfactory Sensory Neurons in Intact Neuroepithelium: Functional Analysis of Neurons Expressing an Identified Odorant Receptor

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Una trampa epigenética estabiliza la expresión singular del receptor olfativo.

David B Lyons¹, William E Allen, Tracie Goh

¹Tetrad Program, University of California, San Francisco, San Francisco, CA 94158, USA.

|July 23, 2013

Resumen

Este resumen es generado por máquina.

La histona demetilasa LSD1 y la adenilil ciclasa 3 (Adcy3) controlan la expresión de los receptores olfativos (OR). Adcy3 desregula la LSD1, estabilizando la expresión OR en las neuronas sensoriales olfativas (OSN).

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Área de la Ciencia:

La neurociencia es la neurociencia.
Biología Molecular Biología Molecular
La epigenética es la epigenética.

Sus antecedentes:

Los mecanismos moleculares que gobiernan la expresión génica del receptor olfativo (OR) en los mamíferos siguen siendo en gran medida desconocidos.
Comprender cómo las neuronas sensoriales olfativas (OSN) logran la expresión OR singular es crucial para la función del sistema olfativo.

Objetivo del estudio:

Aclarar los mecanismos moleculares que regulan el inicio y la estabilización de la expresión de los receptores olfativos (OR).
Identificar las vías de señalización clave involucradas en la regulación epigenética de la elección de OR en las ROS.

Principales métodos:

Investigó las funciones de la histona demetilasa LSD1 y la adenilil ciclasa 3 (Adcy3) en la expresión de OR.
Analizó los patrones de expresión transitorios y las interacciones funcionales de LSD1 y Adcy3 en OSNs.
Examinó la cascada de señalización que involucra la diferenciación LSD1, Adcy3 y OSN.

Principales resultados:

Se requiere la expresión transitoria de LSD1 para iniciar la transcripción de OR, mientras que su regulación a la baja es esencial para la expresión de OR estable.
La expresión dependiente de OR de Adcy3 actúa como un sensor y transmisor de retroalimentación, mediando la regulación a la baja de LSD1.
Adcy3 promueve la diferenciación de OSN y bloquea el estado epigenético de la OR elegida, asegurando la expresión singular.

Conclusiones:

Una nueva cascada de señalización de tres nodos que involucra a LSD1 y Adcy3 regula la expresión de OR.
Esta cascada estabiliza la expresión OR singular al bloquear epigenéticamente el alelo elegido y evitar una mayor activación de OR.
Los hallazgos proporcionan información crítica sobre el control epigenético de la expresión génica y la diferenciación neuronal en el sistema olfativo.