Quality-controlled ceramide-based GPI-anchored protein sorting into selective ER exit sites.

Cell reports 2022 May 03

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Glycosylphosphatidylinositol-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. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Sofia Rodriguez-Gallardo, Susana Sabido-Bozo, Atsuko Ikeda, Misako Araki, Kouta Okazaki, Miyako Nakano, Auxiliadora Aguilera-Romero, Alejandro Cortes-Gomez, Sergio Lopez, Miho Waga, Akihiko Nakano, Kazuo Kurokawa, Manuel Muñiz, Kouichi Funato. Quality-controlled ceramide-based GPI-anchored protein sorting into selective ER exit sites. Cell reports. 2022 May 03;39(5):110768