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In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes
Published on: August 13, 2012
El control de la conductividad del cloruro CFTR por los niveles de ATP a través de la unión no hidrolítica
1Division of Biomedical Sciences, University of California, Riverside 92521.
Nature
|November 5, 1992
Resumen
Los canales de cloruro del regulador de conductividad transmembrana de la fibrosis quística (CFTR) requieren niveles normales de ATP para su activación en los conductos sudoríparos. Esta dependencia pasiva del ATP protege los tejidos del agotamiento energético al reducir el transporte de cloruro.
Área de la Ciencia:
- Biología molecular La biología molecular.
- Fisiología Fisiología Fisiología.
- La bioquímica es la bioquímica.
Sus antecedentes:
- El regulador de conductividad transmembrana de la fibrosis quística (CFTR) está implicado en la fibrosis quística.
- La CFTR funciona como un canal de cloruro de pequeña conductividad activado por la fosforilación.
- El papel del ATP en la activación de la CFTR, en particular la hidrólisis del ATP, sigue sin estar claro.
Objetivo del estudio:
- Para investigar el mecanismo de activación de la CFTR en los conductos sudoríparos.
- Para determinar la relación entre los niveles intracelulares de ATP y la conductancia de cloruro de CFTR.
- Para aclarar el papel del ATP en la función del canal CFTR.
Principales métodos:
- Experimentos de mutación específicos del sitio experimentos de mutación específicos del sitio.
- Ensayos de reconstitución de la membrana.
- Medición de la conductividad del cloruro en los conductos sudoríparos.
- Evaluación de las concentraciones intracelulares de ATP.
Principales resultados:
- La conductividad del cloruro CFTR en los conductos sudoríparos requiere concentraciones intracelulares normales de ATP (alrededor de 5 mM) para su activación.
- La activación parece estar mediada por un mecanismo no hidrolítico, posiblemente alostérico.
- Esta dependencia pasiva del ATP vincula directamente los niveles de energía celular con el transporte de cloruro.
Conclusiones:
- La activación de la CFTR depende pasivamente de los niveles celulares de ATP, no de la hidrólisis de ATP.
- Este mecanismo sirve como una respuesta adaptativa para prevenir el daño tisular por el agotamiento excesivo de la energía.
- El agotamiento modesto del ATP celular reduce significativamente las demandas de energía al disminuir la conductividad del cloruro.
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