Regulation of GPI structural remodeling by protein N-glycosylation (Kinoshita Lab, in J. Cell Biol.)

Most proteins receive various modifications after their synthesis, called post-translational modifications, which regulate protein folding, function and localization. On the cell surface, there are a number of proteins modified by a glycolipid named glycosylphosphatidylinositol (GPI). GPI anchoring of proteins is a post-translational modification well conserved among eukaryotes. So far, we clarified that GPI structures are processed during the transport and the structural remodeling is required for the transport and localization of GPI-anchored proteins. However, it was little known how the GPI structural remodeling is regulated.

In this study, we tried to reveal the regulatory mechanisms of a GPI structural remodeling (GPI-inositol deacylation) using genetic screening. We found that protein asparagine (N)-glycosylations, which are another types of post-translational modifications, regulate GPI-inositol deacylation. N-glycans on proteins play critical roles in protein folding in the endoplasmic reticulum (ER). A molecular chaperone, calnexin, was specifically associated with GPI-anchored proteins, dependent upon N-glycan and GPI moieties. The interaction assisted temporal ER retention of GPI-anchored proteins, and facilitated efficient GPI-inositol deacylation. Once the system is disrupted by chronic ER stress, unprocessed GPI-anchored proteins were exposed on the cell surface. These results indicated that N-glycans participate in quality control and temporal ER retention of GPI-anchored proteins, ensuring their correct folding and GPI processing before exiting from the ER.


This work was performed by collaboration with Dr. Taroh Kinoshita’s laboratory (Yabumoto Department of Intractable Disease Research), Dr. Morihisa Fujita’s group (School of Biotechnology, Jiangnan University, Wuxi, China) and Dr. Shota Nakamura’s group (Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University).


This article was published online in The Journal of Cell Biology, Dec 18, 2017.

N-Glycan-dependent protein folding and endoplasmic reticulum retention regulate GPI-anchor processing.