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

Description

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.

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Japan Society for the Promotion of Science JP19H02922, JP25221103, JP17H06420, JP18H0527

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Ministerio de Ciencia e Innovación PID2020-119505GB-I00, AEI/10.13039/501100011033

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Junta de Andalucía ERDF PY20_01240, US- 1380893

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Universidad de Sevilla VIPPIT-2020-I.5

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