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La regulación de la proteostasis de los organismos mediante la señalización de chaperones transcelulares
Patricija van Oosten-Hawle1, Robert S Porter, Richard I Morimoto
1Department Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA.
Cell
|June 11, 2013
Resumen
Los organismos mantienen la salud de las proteínas a través de una respuesta al estrés sistémico. La mejora de la proteína de choque térmico 90 (HSP90) en un tejido puede proteger a otros, revelando un sistema de vigilancia transcelular.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología molecular La biología molecular.
- Genética La genética.
Sus antecedentes:
- Los metazoos se enfrentan al desafío de mantener la proteostasis del organismo a pesar de los diversos proteomas específicos de los tejidos.
- El estrés proteotóxico puede surgir de proteínas mal plegadas, amenazando la salud celular y del organismo.
- Las chaperonas, como la proteína de choque térmico 90 (HSP90), son cruciales para el plegamiento adecuado de las proteínas.
Objetivo del estudio:
- Para investigar los mecanismos de la proteostasis sistémica en los metazoos.
- Para determinar si el mal plegamiento de proteínas localizadas puede inducir respuestas de estrés en todo el organismo.
- Para aclarar el papel de HSP90 y la comunicación intercelular en el mantenimiento de la proteostasis.
Principales métodos:
- Utilizado *C. elegans* como organismo modelo para estudiar el plegamiento de proteínas y respuestas al estrés.
- Expresión inducida de proteínas metastables en las células musculares para imitar el estrés proteotóxico.
- Manipular la expresión de HSP90 en diferentes tejidos (músculo, intestino, neuronas).
- Investigó el papel del factor de transcripción PHA-4 en la regulación de la expresión de HSP90.
Principales resultados:
- La expresión de proteínas metastables en las células musculares desencadenó una respuesta al estrés sistémico en múltiples tejidos.
- La expresión mejorada de HSP90 en el músculo, el intestino o las células neuronales suprimió efectivamente el mal plegamiento de proteínas en el músculo.
- Este control celular no autónomo de HSP90 está mediado por una retroalimentación transcripcional regulada por el factor de transcripción PHA-4.
- Se demostró una vía de señalización de acompañante transcelular crucial para la proteostasis del organismo.
Conclusiones:
- El mal plegamiento de proteínas localizadas puede inducir una respuesta sistémica de chaperón no autónoma celular.
- La comunicación entre los tejidos, regulada por el PHA-4, es vital para mantener la proteostasis del organismo.
- Esta señalización transcelular proporciona una base para la vigilancia sensible al estrés del organismo.
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