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Las palmitoil aciltransferasas controlan la localización de la membrana del DNAJC5 para regular la secreción de
Yue Xu1, Robbins Puthenveetil2, Juhyung Lee1
1Laboratory of Molecular Biology, National Institute of Diabetes, Digestive, and Kidney Diseases, Bethesda, Maryland, USA.
Traffic (Copenhagen, Denmark)
|February 9, 2026
Resumen
La secreción de proteína mal plegada (MAPS) involucra a DNAJC5, una proteína que puede ser palmitoilada. La palmitoilación de DNAJC5 por DHHC11 mejora su asociación de Golgi y impulsa la secreción de proteínas no convencionales.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La secreción de proteínas no convencionales (UcPS) permite a las células secretar proteínas que carecen de secuencias de señales.
- La secreción de proteína asociada al plegamiento incorrecto (MAPS) es una vía de UcPS que involucra a HSP70 y DNAJC5.5.
- DNAJC5 es un co-chaperón asociado con HSP70 en MAPS.
Objetivo del estudio:
- Para investigar el papel de las modificaciones post-traducionales de DNAJC5 en MAPS.
- Identificar las enzimas responsables de la modificación de DNAJC5 y su impacto en la secreción.
- Determinar las regiones específicas de DNAJC5 críticas para su localización y secreción.
Principales métodos:
- Cultivo y transfección de células humanas.
- Análisis de la palmitoilación de proteínas utilizando enzimas DHHC.
- Estudios de mutagenesis para identificar los dominios funcionales del ADNJC5.5.
- Microscopía confocal para evaluar la localización subcelular (asociación de Golgi).
- Medición de los niveles de secreción de proteínas.
Principales resultados:
- DNAJC5 es palmitoylado por múltiples DHHC palmitoil aciltransferasas en las células humanas.
- La sobreexpresión de DHHC11 conduce al enriquecimiento de Golgi de DNAJC5 y al aumento de la secreción.
- Un módulo mínimo de DNAJC5 (DC95) que contiene el dominio de la cadena de cisteína es suficiente para la palmitoilación, la translocación de Golgi y la secreción.
- Residuos específicos dentro o flanqueando el dominio de la cadena de cisteína son esenciales para estos procesos.
Conclusiones:
- La palmitoilación es un mecanismo regulador clave para la función de DNAJC5 en MAPS.
- Los sitios de palmitoilación y las secuencias adyacentes dictan la localización subcelular de DNAJC5 y su papel en UcPS.
- Este estudio aclara un nuevo mecanismo regulador que controla la secreción no convencional de proteínas mal plegadas.
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