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Transfer of Mammary Gland-forming Ability Between Mammary Basal Epithelial Cells and Mammary Luminal Cells via Extracellular Vesicles/Exosomes
Published on: June 3, 2017
La ceramida desencadena el brote de las vesículas exosómicas en endosomas multivesiculares
Katarina Trajkovic1, Chieh Hsu, Salvatore Chiantia
1Centre for Biochemistry and Molecular Cell Biology, University of Göttingen, 37073 Göttingen, Germany.
Science (New York, N.Y.)
|March 1, 2008
Resumen
El estudio revela que la ceramida, un esfingolipido, impulsa la formación de exosomas desde las membranas endosomales, independientemente de la maquinaria ESCRT. Este hallazgo revela una nueva vía para el transporte intraendosómico y la biogénesis exosómica.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- Los endosomas multivesiculares generan vesículas intraluminales (VLI) clasificadas para la degradación lisosómica o la secreción exosómica.
- Los mecanismos que rigen la clasificación de la membrana endosómica en distintas poblaciones de ILV siguen sin estar claros.
Objetivo del estudio:
- Para dilucidar los mecanismos de clasificación de la membrana en vesículas intraluminales para la formación de exosomas.
- Identificar a los actores moleculares clave en la biogénesis de los exosomas.
Principales métodos:
- Se investigó la segregación de la carga en subdominios de la membrana endosómica.
- Evaluó el papel de la maquinaria ESCRT y la ceramida esfingolipídica en la formación de ILV.
- Se analizó el enriquecimiento de ceramida en exosomas purificados.
- Se examinó el efecto de la inhibición de la esfingomielinasa neutra en la liberación de exosomas.
Principales resultados:
- La carga está segregada en subdominios distintos en la membrana endosómica.
- La transferencia de dominios asociados al exosoma en el lumen del endosoma requiere ceramida, no ESCRT.
- Los exosomas purificados muestran enriquecimiento en ceramida.
- La inhibición de las esfingomielinasas neutrales reduce la liberación de los exosomas.
Conclusiones:
- Establece una vía dependiente de la ceramida para el transporte de la membrana intraendosómica y la formación de exosomas.
- Destaca el papel crítico de los esfingolipidos en la biogénesis del exosoma.
- Sugiere un nuevo mecanismo para la secreción exosómica independiente de la ESCRT.
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