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El control post-traducional de la dinámica temporal de la actividad del factor de transcripción regula la

Xiao-Jiang Quan¹, Liqun Yuan², Luca Tiberi³

¹VIB Center for the Biology of Disease, VIB, 3000 Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium.

|January 30, 2016

Resumen

Un interruptor posterior a la traducción, la fosforilación, controla la duración de la actividad de la proteína proneural, crucial para el desarrollo neuronal. La alteración de este interruptor afecta el número de neuronas y el destino.

Área de la Ciencia:

Biología del desarrollo
Biología molecular
La neurociencia

Sus antecedentes:

La neurogénesis se basa en las proteínas proneurales expresadas transitoriamente, que son reguladores de la transcripción bHLH.
Comprender la regulación de la duración de la actividad de las proteínas proneurales es clave para comprender el desarrollo neuronal adecuado.

Objetivo del estudio:

Identificar y caracterizar un mecanismo post-traducional conservado que controla la duración de la actividad de las proteínas proneurales.
Investigar el papel de este mecanismo en la regulación del número de neuronas y el destino durante el desarrollo.

Principales métodos:

Utilizó la edición del genoma en Drosophila para estudiar la proteína Atonal.
Se han investigado los sitios de fosforilación en las proteínas proneurales (Scute, Atonal, Neurogenin2).
Cambios analizados en la dinámica de la expresión génica y el desarrollo neuronal al alterar los estados de fosforilación.

Principales resultados:

Descubrió un interruptor de fosforilación conservado que regula la transición de las proteínas proneurales de estados activos a inactivos mediante la modulación de la unión al ADN.
Se ha demostrado que la inactivación de la proteína atonal en Drosophila está mediada por la fosforilación, independientemente de los niveles de ARNm.
Se demostró que la inhibición de la fosforilación de un residuo de serina conservado conduce a defectos en el número y destino neuronales.
Se observó que una sola sustitución de aminoácidos (serina por treonina) altera la duración de la actividad atonal y causa defectos de destino neuronal.

Conclusiones:

La fosforilación posterior a la traducción es un interruptor crítico que rige la duración de la actividad de la proteína proneural.
Este mecanismo de fosforilación es esencial para el control preciso del desarrollo neuronal, incluida la determinación del número neuronal y el destino celular.
Los hallazgos destacan un mecanismo regulador conservado con implicaciones para la comprensión de los procesos de desarrollo neurológico.

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