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La nicastrina funciona como un receptor del sustrato de la gamma-secretasa
Sanjiv Shah1, Sheu-Fen Lee, Katsuhiko Tabuchi
1Center for Basic Neuroscience, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Cell
|August 13, 2005
Resumen
Nicastrin actúa como un receptor para la proteína precursora amiloide (APP) y sustratos Notch. Su ectodominio se une a sustratos escindidos, reclutándolos para el complejo gamma-secretasa para la proteólisis intramembrana.
Área de la Ciencia:
- Biología molecular y celular Biología molecular y celular.
- La neurociencia es la neurociencia.
Sus antecedentes:
- La gamma-secretasa lleva a cabo la escisión intramembrana de la proteína precursora del amiloide (APP) y Notch.
- Nicastrin es un componente conocido del complejo gamma-secretasa con un papel indefinido.
Objetivo del estudio:
- Para aclarar la función de la nicastrina dentro del complejo gamma-secretasa.
- Para investigar cómo se reclutan los sustratos para la escisión mediada por gamma-secretasa.
Principales métodos:
- Investigó la interacción entre el ectodominio de la nicastrina y el sustrato amino termini.
- Utilizó estrategias químicas y de bloqueo de anticuerpos.
- Se realizó un análisis de mutación del ectodominio de la nicastrina.
Principales resultados:
- El ectodominio de la nicastrina se une al terminal amino recién generado de los sustratos APP y Notch escindidos.
- Esta unión facilita el reclutamiento de sustratos en el complejo gamma-secretasa.
- El bloqueo de esta interacción o la mutación de la ectodomaína de nicastrina reduce la unión y la escisión del sustrato.
Conclusiones:
- La nicastrina funciona como un receptor para los trozos amino-terminales de las proteínas transmembranales de tipo I después del derramamiento del ectodominio.
- Nicastrin presenta estos sustratos a la gamma-secretasa, promoviendo su proteólisis intramembrana.
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