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N-Glycan-dependent protein folding and endoplasmic reticulum retention regulate GPI-anchor processing
Yi-Shi Liu1, Xin-Yu Guo1, Tetsuya Hirata2,3
1Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Jiangsu, China.
The Journal of Cell Biology
|December 20, 2017
Summary
Post-translational modification of glycosylphosphatidylinositol-anchored proteins (GPI-APs) involves PGAP1-mediated deacylation. Calnexin aids this process, crucial for protein folding and transport from the ER.
Area of Science:
- Cell Biology
- Molecular Biology
- Protein Biochemistry
Background:
- Glycosylphosphatidylinositol (GPI) anchoring is a vital posttranslational modification in the endoplasmic reticulum (ER).
- The enzyme post-GPI attachment to proteins 1 (PGAP1) removes an acyl chain from the GPI inositol, facilitating the transition of GPI-anchored proteins (GPI-APs) from folding to transport states.
Purpose of the Study:
- To identify factors regulating GPI-inositol deacylation.
- To elucidate the role of calnexin in the quality control of GPI-APs.
Main Methods:
- Haploid genetic screens were employed to identify genes involved in GPI-inositol deacylation.
- Co-immunoprecipitation was used to assess the association of calnexin with GPI-APs.
- Analysis of GPI-AP processing under ER stress conditions.
Main Results:
- Seven genes regulating GPI-inositol deacylation were identified.
- Impairment of the calnexin cycle led to inefficient GPI-inositol deacylation.
- Calnexin specifically binds to GPI-APs, dependent on N-glycan and GPI moieties, and promotes PGAP1 activity.
- Inositol-acylated GPI-APs accumulated on the cell surface during chronic ER stress.
Conclusions:
- N-glycans are critical for the ER quality control and retention of GPI-APs, ensuring proper folding and GPI processing.
- Calnexin plays a key role in facilitating GPI-inositol deacylation by PGAP1.
- Disruption of ER homeostasis exposes unprocessed GPI-APs on the cell surface.
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