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

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-A...

Full description

Bibliographic Details
Authors: Rodríguez Gallardo, Sofía, Sabido Bozo, Susana, Ikeda, Atsuko, Araki, Misako, Okazaki, Kouta, Nakano, Miyako, Aguilera Romero, María Auxiliadora, Cortés Gómez, Alejandro, López Martín, Sergio, Waga, Miho, Nakano, Akihiko, Kurokawa, Kazuo, Muñiz Guinea, Manuel, Funato, Kouichi
Format: article
Status:Published version
Publication Date:2022
Country:España
Institution:Universidad de Sevilla (US)
Repository:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/133541
Online Access:https://hdl.handle.net/11441/133541
https://doi.org/10.1016/j.celrep.2022.110768
Access Level:Open access
Keyword:Ceramide remodeling
CP: Cell biology
CP: Molecular biology
Endoplasmic reticulum
Glycan remodeling
GPI-anchored protein
Protein sorting
Quality control
Yeast Saccharomyces cerevisiae
Description
Summary: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.