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Dissection of Local Ca2+ Signals in Cultured Cells by Membrane-targeted Ca2+ Indicators
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La modulación dependiente de AMP/GMP cíclica de los canales de Ca2+ establece la polaridad del giro del cono de
Makoto Nishiyama1, Akemi Hoshino, Lily Tsai
1Department of Biochemistry, New York University School of Medicine, New York, New York 10016-6402, USA.
Nature
|June 27, 2003
Resumen
La relación entre la AMP cíclica (cAMP) y la GMP cíclica (cGMP) determina la dirección de orientación del axón. Las altas proporciones de cAMP / cGMP promueven la atracción, mientras que las bajas proporciones impulsan la repulsión, lo que afecta el desarrollo neuronal.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Los segundos mensajeros intracelulares como los nucleótidos cíclicos y los iones de calcio (Ca2+) regulan la orientación de los axones.
- El mecanismo de interacción preciso de estos mensajeros en la determinación de la polaridad de guía bidireccional del axón sigue sin estar claro.
Objetivo del estudio:
- Investigar cómo interactúan la señalización de adenosina monofosfato cíclico (cAMP) y guanosina monofosfato cíclico (cGMP) para controlar la polaridad del axón inducido por netrina-1.
- Aclarar el papel de estos segundos mensajeros en la modulación de la actividad de los canales de calcio dentro de los conos de crecimiento neuronal.
Principales métodos:
- Grabaciones con pinzas de parche de células enteras de corrientes de Ca2+ en conos de crecimiento de neuronas espinales de Xenopus.
- Análisis de la actividad de los nucleótidos cíclicos y su efecto en la función del canal Ca2+ (LCC) de tipo L.
- Investigando el papel de la señalización cGMP en la repulsión mediada por netrina-1 a través del complejo receptor DCC-UNC5.
Principales resultados:
- La relación entre la actividad de cAMP y cGMP dicta la polaridad de la orientación del axón inducida por la netrina-1, con relaciones altas que favorecen la atracción y relaciones bajas que favorecen la repulsión.
- La señalización de nucleótidos cíclicos modula directamente la actividad del canal Ca2+ de tipo L en los conos de crecimiento.
- La señalización cGMP suprime la actividad de LCC inducida por la netrina-1 y es esencial para la repulsión del cono de crecimiento mediada por DCC-UNC5.
Conclusiones:
- Se ha establecido un vínculo directo entre las vías de señalización cAMP y cGMP y la actividad del canal Ca2+ en los conos de crecimiento.
- Estos hallazgos revelan un mecanismo clave asociado a la membrana para la transducción de señales en la orientación bidireccional de los axones.
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