Rodriguez-Gallardo, SofiaSabido-Bozo, SusanaIkeda, AtsukoAraki, MisakoOkazaki, KoutaNakano, MiyakoAguilera-Romero, AuxiliadoraCortes-Gomez, AlejandroLopez, SergioWaga, MihoNakano, AkihikoKurokawa, KazuoMuñiz, ManuelFunato, Kouichi2023-05-032023-05-032022http://hdl.handle.net/10668/22076Glycosylphosphatidylinositol-anchored proteins (GPI-APs) exit the endoplasmic reticulum (ER) through a specialized export pathway in the yeast Saccharomyces cerevisiae. We have recently shown that a very-long acyl chain (C26) ceramide present in the ER membrane drives clustering and sorting of GPI-APs into selective ER exit sites (ERES). Now, we show that this lipid-based ER sorting also involves the C26 ceramide as a lipid moiety of GPI-APs, which is incorporated into the GPI anchor through a lipid-remodeling process after protein attachment in the ER. Moreover, we also show that a GPI-AP with a C26 ceramide moiety is monitored by the GPI-glycan remodelase Ted1, which, in turn, is required for receptor-mediated export of GPI-APs. Therefore, our study reveals a quality-control system that ensures lipid-based sorting of GPI-APs into selective ERESs for differential ER export, highlighting the physiological need for this specific export pathway.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/CP: Cell biologyCP: Molecular biologyGPI-anchored proteinceramide remodelingendoplasmic reticulumglycan remodelingprotein sortingquality controlyeast Saccharomyces cerevisiaeCeramidesEndoplasmic ReticulumGPI-Linked ProteinsGlycosylphosphatidylinositolsProtein TransportSaccharomyces cerevisiaeresearch article35508142open access10.1016/j.celrep.2022.1107682211-1247http://www.cell.com/article/S2211124722005320/pdf