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La dependencia de la calmodulina de la señalización presináptica del receptor metabotrópico del glutamato en los
V O'Connor1, O El Far, E Bofill-Cardona
1Department of Neurochemistry, Max Planck Institute for Brain Research, Deutschordenstrasse 46, 60528 Frankfurt, Germany.
Science (New York, N.Y.)
|November 5, 1999
Resumen
Los receptores presinápticos metabotrópicos del glutamato (mGluRs) controlan la neurotransmisión. La unión calcio-calmodulina libera subunidades de la proteína G, lo que permite a las mGluR inhibir la neurotransmisión excitatoria.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- La señalización celular.
Sus antecedentes:
- Los receptores presinápticos metabotrópicos del glutamato (mGluRs) regulan la neurotransmisión glutamatérgica.
- Los mGluR del grupo III poseen una cola carboxilo-terminal intracelular involucrada en las interacciones proteicas.
Objetivo del estudio:
- Aclarar el mecanismo por el cual los mGluR del grupo III modulan las corrientes iónicas y la neurotransmisión.
- Para investigar las funciones de la calmodulina y las subunidades beta de la proteína G en la función mGluR.
Principales métodos:
- Utilizando mutaciones para interrumpir los sitios de unión a la calmodulina en el grupo III mGluRs.
- El empleo de antagonistas de la calmodulina para inhibir la función de la calmodulina.
- Evaluar el impacto de estas manipulaciones en la modulación mediada por proteínas G de las corrientes iónicas y la neurotransmisión excitatoria.
Principales resultados:
- Las mutaciones que afectan la unión a la calmodulina y los antagonistas de la calmodulina inhiben la modulación mediada por proteínas G de las corrientes iónicas por mGluR 7.
- Los antagonistas de la calmodulina también impidieron la inhibición de la neurotransmisión excitatoria mediada por mGluRs presinápticos.
- Estos hallazgos indican una unión mutuamente exclusiva de la calmodulina y las subunidades beta de la proteína G a la cola C de mGluR.
Conclusiones:
- Se ha identificado un nuevo mecanismo para la modulación presináptica que involucra a la Ca(2+) -calmodulina.
- Ca2+) -calmodulina es esencial para la liberación de las subunidades de la proteína G beta-gama del grupo III mGluRs.
- Esta liberación es necesaria para mediar la autoinhibición glutamatérgica a través de mGluRs presinápticos.
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