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Mecanismo de la interacción del cloruro con el neurotransmisor: los simportadores de sodio
Elia Zomot1, Annie Bendahan, Matthias Quick
1Department of Biochemistry, Hebrew University Hadassah Medical School, POB 12272, Jerusalem 91120, Israel.
Nature
|August 21, 2007
Resumen
Neurotransmisor: los simportadores de sodio (NSS) utilizan iones de cloruro para el transporte de neurotransmisores. La introducción de cargas negativas en el transportador imita el cloruro.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- Neurotransmisores: los simportadores de sodio (NSS) son cruciales para la neurotransmisión y las dianas de los fármacos.
- Las SSN eucariotas transportan cloruro con neurotransmisores, a diferencia de las SSN bacterianas.
- El papel y el sitio de unión del cloruro en el transporte de NSS siguen sin estar claros.
Objetivo del estudio:
- Para aclarar el papel preciso del cloruro en el transporte de neurotransmisores por NSS.
- Para identificar el sitio de unión del cloruro dentro de los transportadores NSS.
Principales métodos:
- Introducción de aminoácidos cargados negativamente en el transportador de GABA GAT-1 (SLC6A1) en los supuestos sitios de unión al sodio.
- Evaluación del flujo y el intercambio de GABA en GAT-1, GAT4 (SLC6A11) y DAT (SLC6A3) mutados.
- Las mutaciones recíprocas se introdujeron en el NSS bacteriano (LeuT, Tyt1) para la comparación.
Principales resultados:
- Las mutaciones en GAT-1, GAT4 y DAT dieron como resultado un transporte en gran medida independiente del cloruro.
- La reducción del pH interno estimuló el flujo neto, pero no el intercambio en el GAT-1 mutado.
- Las mutaciones recíprocas en el NSS bacteriano conferían dependencia del cloruro.
Conclusiones:
- Una carga negativa, ya sea del cloruro o del transportador, es esencial para la unión y translocación de los neurotransmisores en el NSS.
- Esta carga negativa probablemente contrarresta la carga positiva de los iones de sodio co-transportados.
- Los hallazgos proporcionan información sobre el mecanismo de la NSS y el potencial desarrollo de fármacos.
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