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TrkB media la supervivencia y la proliferación dependientes de BDNF/NT-3 en los fibroblastos que carecen del receptor
David J Glass1, Steven H Nye, Petros Hantzopoulos
1Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591.
Cell
|July 26, 1991
Resumen
El factor neurotrófico derivado del cerebro (BDNF) y la neurotropina-3 (NT-3) promueven la supervivencia y la proliferación celular a través de la señalización TrkB. El receptor NGF de baja afinidad (LNGFR) no es esencial para estas respuestas neurotrofinas.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- La señalización celular de las células.
Sus antecedentes:
- Las neurotropinas, incluido el factor de crecimiento nervioso (NGF), el factor neurotrófico derivado del cerebro (BDNF), la neurotropina-3 (NT-3) y la neurotropina-4 (NT-4), son cruciales para la supervivencia neuronal.
- Estos factores señalan a través de la familia Trk de las receptoras tirosina quinasas, potencialmente con el receptor NGF de baja afinidad (LNGFR).
Objetivo del estudio:
- Investigar el papel de TrkB en la mediación de las respuestas celulares al BDNF y al NT-3.
- Para determinar la necesidad de LNGFR en la señalización de neurotrofinas.
Principales métodos:
- Expresión de TrkB en los fibroblastos 3T3 de los NIH.
- Evaluación de la supervivencia y la proliferación celular en respuesta al BDNF y al NT-3.
- Análisis de las respuestas dosis-dependientes y comparación con la supervivencia neuronal primaria.
Principales resultados:
- La expresión de TrkB en los fibroblastos confería respuestas de supervivencia y proliferación tanto al BDNF como al NT-3, siendo el BDNF un ligando más potente.
- La curva de dosis-respuesta para el BDNF en los fibroblastos que expresan TrkB reflejó la observada para la supervivencia neuronal primaria.
- La ausencia de LNGFR en el sistema de fibroblastos indicó que no es esencial para la señalización fisiológica de las neurotrofinas.
Conclusiones:
- TrkB es un mediador clave de la supervivencia y la señalización de la proliferación aguas abajo de BDNF y NT-3.
- El LNGFR no es indispensable para mediar los efectos de las neurotrofinas en concentraciones fisiológicas.
- Los hallazgos proporcionan información sobre las vías de señalización de las neurotrofinas y los mecanismos de muerte celular neuronal.
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