Curr Biol. 2014 Dec 30. pii: S0960-9822(14)01500-0. doi: 10.1016/j.cub.2014.11.039


Javier Manzano-Lopez, Ana M. Perez-Linero, Auxiliadora Aguilera-Romero, Maria E. Martin, Tatsuki Okano, Daniel Varon Silva, Peter H. Seeberger, Howard Riezman, Kouichi Funato, Veit Goder, Ralf E. Wellinger, Manuel Muñiz


Background: Export from the ER is an essential process driven by the COPII coat, which forms vesicles at ER exit sites (ERESs) to transport mature secretory proteins to the Golgi. Although the basic mechanism of COPII assembly is known, how COPII machinery is regulated to meet varying celular secretory demands is unclear. Results: Here, we report a specialized COPII system that is actively recruited by luminal cargo maturation. Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are luminal secretory proteins anchored to the membrane by the glycolipid GPI. After protein attachment in the ER lumen, lipid and glycan parts of the GPI anchor are remodeled. In yeast, GPI-lipid remodeling concentrates GPI-APs into specific ERESs. We found that GPI-glycan remodeling induces subsequent recruitment of the specialized ER export machinery that enables vesicle formation from these specific ERESs. First, the transmembrane cargo receptor p24 complex binds GPI-APs as a lectin by recognizing the remodeled GPI-glycan. Binding of remodeled cargo induces the p24 complex to recruit the COPII subtype Lst1p, specifically required for GPI-AP ER export. Conclusions: Our results show that COPII coat recruitment by cargo receptors is not constitutive but instead is actively regulated by binding of mature ligands. Therefore, we reveal a novel functional link between luminal cargo maturation and COPII vesicle budding, providing a mechanism to adjust specialized COPII vesicle production to the amount and quality of their luminal cargos that are ready for ER exit. This helps to understand how the ER export machinery adapts to different needs for luminal cargo secretion.


La exportación de proteínas del retículo endoplásmico (RE) es un proceso esencial en las células eucariotas, que se basa en la formación de vesículas de transporte por el complejo de cubierta COPII en los sitios de salida. Muchas de las proteínas carga necesitan receptores para ser incorporadas eficientemente a las vesículas COPII nacientes. En este trabajo, mostramos que dichos receptores no reclutan a la cubierta COPII constitutivamente, sino que lo hacen de manera regulada sólo cuando han unido previamente a su carga proteica madura. Nuestros resultados revelan un nuevo mecanismo regulador que ajusta la producción de vesículas COPII a la cantidad y calidad de proteínas carga preparadas para salir del RE. Este estudio contribuye a comprender a nivel molecular cómo la maquinaria de exportación del RE se adapta a las necesidades cambiantes de secreción.



La vida eucariota depende de la organización espacio-temporal de los sistemas de membrana celulares, la cual se alcanza en gran medida gracias al transporte vesicular. El objetivo principal del grupo dirigido por el Dr. Manuel Muñiz es comprender a nivel molecular los procesos fundamentales de transporte vesicular que tienen lugar al comienzo de la ruta secretora entre el retículo endoplásmico y el complejo de Golgi. Para ello, se pretende descifrar el papel clave de los receptores de transporte en la regulación de la organización funcional de ambos orgánulos secretores. El Dr. Muñiz es profesor del Departamento de Biología Celular de la Facultad de Biología de la Universidad de Sevilla e Investigador adscrito al IBIS (Instituto de Biomedicina de Sevilla).

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