Rodriguez-Gallardo S, Kurokawa K, Sabido-Bozo S, Cortes-Gomez A, Ikeda A, Zoni V, Aguilera-Romero A, Perez-Linero AM, Lopez S, Waga M, Araki M, Nakano M, Riezman H, Funato K, Vanni S, Nakano A, Muñiz M. Ceramide chain length-dependent protein sorting into selective endoplasmic reticulum exit sites. Sci Adv. 2020 Dec 11;6(50):eaba8237. doi: 10.1126/sciadv.aba8237. PMID: 33310842; PMCID: PMC7732199.


Sofia Rodriguez-Gallardo, Kazuo Kurokawa, Susana Sabido-Bozo, Alejandro Cortes-Gomez, Atsuko Ikeda, Valeria Zoni, Auxiliadora Aguilera-Romero, Ana Maria Perez-Linero, Sergio Lopez, Miho Waga, Misako Araki, Miyako Nakano, Howard Riezman, Kouichi Funato, Stefano Vanni, Akihiko Nakano, Manuel Muñiz.


Protein sorting in the secretory pathway is crucial to maintain cellular compartmentalization and homeostasis. In addition to coat-mediated sorting, the role of lipids in driving protein sorting during secretory transport is a longstanding fundamental question that still remains unanswered. Here, we conduct 3D simultaneous multicolor high-resolution live imaging to demonstrate in vivo that newly synthesized glycosylphosphatidylinositol-anchored proteins having a very long chain ceramide lipid moiety are clustered and sorted into specialized endoplasmic reticulum exit sites that are distinct from those used by transmembrane proteins. Furthermore, we show that the chain length of ceramide in the endoplasmic reticulum membrane is critical for this sorting selectivity. Our study provides the first direct in vivo evidence for lipid chain length–based protein cargo sorting into selective export sites of the secretory pathway.


Este estudio demuestra por primera vez de forma concluyente que los lípidos de membrana juegan un papel esencial en la distribución selectiva de las proteínas en la ruta secretora. Mediante microscopía 3D de alta resolución en célula viva, los autores revelan la importancia crítica de las ceramidas de cadena muy larga en la exportación diferencial de las proteínas ancladas al glicolípido GPI, que utilizan sitios de salida del retículo endoplásmico distintos a los usados por las proteínas transmembrana. Además, el trabajo desvela las bases mecanísticas de este proceso de transporte selectivo dependiente de lípidos largos.

Imagen de grupo


Nuestro grupo, dirigido por Manuel Muñiz en el Departamento de Biología Celular de la Facultad de Biología de la Universidad de Sevilla, trata de comprender los principios básicos que gobiernan el tráfico de membranas. En particular, nos interesa dilucidar los mecanismos del transporte selectivo de proteínas que opera en la ruta secretora temprana entre el retículo endoplásmico y el Golgi, y que contribuye de forma esencial a la compartimentalización y homeostasis funcional de la célula eucariota. Para ello realizamos una aproximación multidisciplinar, que incluye una microscopía avanzada de alta resolución, técnicas bioquímicas y moleculares y simulación de dinámica molecular, en combinación con el potente sistema genético de la levadura.

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