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Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
El supresor de la proteína sin pelo participa en la señalización de los receptores de muesca
M E Fortini1, S Artavanis-Tsakonas
1Howard Hughes Medical Institute, Department of Biology, Yale University, New Haven, Connecticut 06536.
Cell
|October 21, 1994
Resumen
Se identificaron mutaciones de ganancia de función en el supresor de Hairless (Su(H), un regulador de señalización Notch. La señalización de la muesca controla la localización de la proteína Su(H), lo que afecta a los eventos nucleares en el desarrollo de la Drosophila.
Área de la Ciencia:
- Biología del desarrollo Biología del desarrollo.
- Genética La genética.
- Biología Molecular Biología Molecular
Sus antecedentes:
- La señalización de muescas es crucial para la determinación del destino celular en el desarrollo.
- El supresor de Hairless (Su(H)) es un factor de transcripción clave en la vía de Notch.
- La comprensión de la regulación de Su(H) proporciona información sobre los procesos de desarrollo.
Objetivo del estudio:
- Para identificar mutaciones que afectan a la señalización de Notch en el desarrollo del ojo de Drosophila.
- Para investigar los mecanismos reguladores de la actividad de la proteína Su(H).
- Para aclarar la relación entre Notch y Su(H) en la localización celular.
Principales métodos:
- Cribado genético en Drosophila melanogaster para aislar alelos de ganancia de función.
- Análisis de las interacciones genéticas específicas del alelo con los componentes de la vía Notch.
- Experimentos de cultivo celular para estudiar la localización de proteínas utilizando ensayos de coexpresión y unión de ligandos.
- Prueba de trampa de interacción de levadura para confirmar las interacciones proteína-proteína.
Principales resultados:
- Se han aislado nuevos alelos de ganancia de función del supresor de Hairless (Su(H)).
- Se han demostrado interacciones específicas de alelos entre Su(H), Notch, Delta, deltex y la mente maestra.
- Se demostró que la señalización de Notch regula la localización de la proteína Su (H) entre el citoplasma y el núcleo.
- Se identificaron las repeticiones intracelulares de Notch cdc10/ankyrin como críticas para la retención citoplasmática de Su(H).
Conclusiones:
- La señalización de la muesca controla directamente la localización celular y la actividad de la proteína de unión al ADN Su(H).
- Este mecanismo pone de relieve cómo la activación de los receptores de superficie celular puede influir en la transcripción nuclear.
- Los hallazgos proporcionan una base molecular para la regulación mediada por Notch de la expresión génica en el desarrollo.
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