Department of Cell Biology, Faculty of Biology, University of Seville and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41012 Seville, Spain.
Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8528, Japan.
Cell Rep. 2022 May 3;39(5):110768. doi: 10.1016/j.celrep.2022.110768.
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.
糖基磷脂酰肌醇锚定蛋白（GPI-APs）通过酵母酿酒酵母中的一种特殊输出途径从内质网（ER）中输出。我们最近表明，内质网膜中存在的非常长链（C26）神经酰胺驱动 GPI-AP 进入选择性内质网出口部位（ERES）的聚类和分拣。现在，我们表明这种基于脂质的 ER 分拣还涉及 C26 神经酰胺作为 GPI-AP 的脂质部分，它在 ER 中附着蛋白质后通过脂质重塑过程被整合到 GPI 锚中。此外，我们还表明，带有 C26 神经酰胺部分的 GPI-AP 受到 GPI-聚糖重塑酶 Ted1 的监测，反过来，Ted1 对于 GPI-AP 的受体介导的输出也是必需的。因此，我们的研究揭示了一种质量控制系统，该系统确保 GPI-AP 基于脂质的分拣进入选择性 ERES，以进行差异 ER 输出，突出了这种特定输出途径的生理需求。
