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La regulación de Siah de Pard3A controla la adhesión de las células neuronales durante la salida de la zona germinal
Jakub K Famulski1, Niraj Trivedi, Danielle Howell
1Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Science (New York, N.Y.)
|November 27, 2010
Resumen
Los científicos descubrieron una nueva vía de señalización que controla cómo las neuronas jóvenes dejan su lugar de nacimiento. Esta vía implica la degradación de la proteína Pard3A por Siah, lo que permite a las neuronas migrar y formar circuitos cerebrales.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología del desarrollo Biología del desarrollo.
- Biología celular Biología celular.
Sus antecedentes:
- La formación de circuitos cerebrales se basa en la migración neuronal precisa y el desarrollo de las sinapsis.
- Los mecanismos que rigen la forma en que las neuronas salen de su nicho de la zona germinal siguen siendo en gran medida desconocidos.
Objetivo del estudio:
- Para investigar la regulación molecular de la neurona del gránulo cerebeloso de la zona germinal salida.
- Identificar las vías de señalización que controlan la salida de las neuronas inmaduras de su nicho de desarrollo.
Principales métodos:
- Se utilizaron ensayos de degradación proteasomal para estudiar la regulación de Pard3A.
- Manipulación genética empleada (ganancia de función/pérdida de función) de Pard3A y Siah.
- Realizó imágenes de lapso de tiempo con una sonda de contacto de células neuronales.
Principales resultados:
- La degradación proteasómica de Pard3A por Siah E3 ubiquitin ligasa regula la salida de la zona germinal.
- Pard3A promueve la salida de la zona germinal al mejorar la adhesión celular a través del reclutamiento de la molécula de adhesión C.
- La ganancia de la función Pard3A o la pérdida de la función Siah conduce a la migración neuronal prematura.
Conclusiones:
- Una nueva vía de señalización Siah-Pard3A controla la salida de la zona germinal dependiente de la adhesión.
- Esta vía es crucial para regular la migración de los progenitores neuronales y las neuronas inmaduras.
- Los hallazgos proporcionan información sobre los procesos fundamentales del desarrollo cerebral y la formación de circuitos.
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