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Diferentes cambios cinéticos en la liberación de neurotransmisores después de la escisión de la proteína SNARE
Takeshi Sakaba1, Alexander Stein, Reinhard Jahn
1Department of Neurobiology and Department of Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen 37077, Germany. tsakaba@gwdg.de
Science (New York, N.Y.)
|July 16, 2005
Resumen
Las neurotoxinas clostridiales cortan las proteínas SNARE, alterando la cinética de liberación de los neurotransmisores. Diferentes toxinas afectan la sensibilidad al calcio y la liberación de las vesículas de manera diferente, revelando roles específicos en la transmisión sináptica.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
Sus antecedentes:
- La liberación de neurotransmisores es esencial para la comunicación neuronal.
- Este proceso es críticamente dependiente de las proteínas SNARE (receptores de proteínas de unión del factor sensible a la N-etilmaleimida soluble).
- Las neurotoxinas clostridiales son ampliamente utilizadas para diseccionar la función de la proteína SNARE.
Objetivo del estudio:
- Investigar las distintas funciones de proteínas SNARE específicas en la liberación de neurotransmisores.
- Para determinar cómo la escisión de diferentes proteínas SNARE por neurotoxinas afecta la cinética de liberación y la sensibilidad al calcio.
Principales métodos:
- Utilizó el cáliz de la terminal presináptica de las ratas.
- Calcio enjaulado empleado para elevar directamente la concentración de calcio intracelular.
- Se administró toxina botulínica A (BoNT/A), toxina botulínica C1 (BoNT/C1) y toxina del tétano (TeNT) para dividir proteínas SNARE específicas.
Principales resultados:
- La escisión de SNAP-25 por BoNT/A reduce significativamente la sensibilidad al calcio para su liberación.
- La escisión de la sintaxina por BoNT/C1 y la sinaptobrevina por TeNT dio como resultado un bloqueo de liberación de todo o nada sin alterar la cinética de las vesículas restantes.
- Cuando la liberación fue estimulada por la afluencia de calcio, BoNT / C1 y TeNT mostraron efectos distintos, lo que sugiere que los impactos de la escisión de la sinaptobrevina en el acoplamiento canal-liberación.
Conclusiones:
- Diferentes proteínas SNARE desempeñan funciones distintas en la regulación de la cinética y la dependencia del calcio de la liberación de neurotransmisores.
- La función de Synaptobrevin parece ser crítica para acoplar el influjo de calcio a través de canales para liberar vesículas competentes.
- La escisión mediada por neurotoxinas proporciona una poderosa herramienta para dilucidar las contribuciones específicas de las proteínas SNARE en la transmisión sináptica.
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