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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
Published on: June 15, 2017
Se requiere la modificación del colesterol del erizo sónico para la actividad de señalización de largo alcance y la
P M Lewis1, M P Dunn, J A McMahon
1Department of Molecular and Cellular Biology, The Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.
Cell
|June 8, 2001
Resumen
La modificación del colesterol de Sonic hedgehog (Shh) es crucial para su rango de señalización durante el desarrollo de las extremidades de los vertebrados. Esta etiqueta lipofílica asegura el patrón anterior-posterior adecuado y la interacción del receptor.
Área de la Ciencia:
- Biología del desarrollo Biología del desarrollo.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- La señalización de Sonic hedgehog (Shh) desde la zona posterior de actividad polarizante (ZPA) dicta la polaridad anterior-posterior en las extremidades de los vertebrados.
- Shh se somete al autoprocesamiento, vinculando covalentemente el colesterol a su fracción de señalización N-terminal (N-Shh(p), atándolo a la membrana celular.
Objetivo del estudio:
- Para investigar el papel de la modificación del colesterol en el patrón mediado por Shh de los dedos del ratón.
- Para entender cómo la modificación lipofílica influye en el rango de señalización Shh y la interacción del receptor.
Principales métodos:
- Análisis de la distribución de N-Shh(p) y la actividad biológica en modelos de desarrollo de extremidades de ratón.
- Comparación de las características de señalización entre el N-Shh modificado por el colesterol (p) y el N-Shh no modificado.
Principales resultados:
- El N-Shh (p) modificado por el colesterol exhibe una distribución y un rango de actividad más amplios, actuando a lo largo de varios cientos de micras.
- El N-Shh no modificado muestra una actividad biológica similar, pero está restringido a la señalización posterior.
- La modificación del colesterol es esencial para el rango de señalización Shh normal y la modulación por el receptor Ptc1.
Conclusiones:
- La modificación lipídica de Shh es crítica para establecer el gradiente de señalización apropiado necesario para el patrón de las extremidades.
- La etiqueta de colesterol extiende el rango de señalización de Shh, asegurando la formación correcta del eje anterior-posterior en el desarrollo de las extremidades.
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