2. Academic Validation
  3. N-Glycan-dependent protein folding and endoplasmic reticulum retention regulate GPI-anchor processing

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

  • J Cell Biol. 2018 Feb 5;217(2):585-599. doi: 10.1083/jcb.201706135.
Yi-Shi Liu 1,  Xin-Yu Guo 1,  Tetsuya Hirata 2 3,  Yao Rong 1,  Daisuke Motooka 2,  Toshihiko Kitajima 1,  Yoshiko Murakami 2 3,  Xiao-Dong Gao 1,  Shota Nakamura 2,  Taroh Kinoshita 4 3,  Morihisa Fujita 5
Affiliations

Affiliations

  • 1 Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Jiangsu, China.
  • 2 Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
  • 3 World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan.
  • 4 Research Institute for Microbial Diseases, Osaka University, Osaka, Japan tkinoshi@biken.osaka-u.ac.jp.
  • 5 Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Jiangsu, China fujita@jiangnan.edu.cn.
PMID: 29255114 DOI: 10.1083/jcb.201706135
Abstract

Glycosylphosphatidylinositol (GPI) anchoring of proteins is a conserved posttranslational modification in the endoplasmic reticulum (ER). Soon after GPI is attached, an acyl chain on the GPI inositol is removed by post-GPI attachment to proteins 1 (PGAP1), a GPI-inositol deacylase. This is crucial for switching GPI-anchored proteins (GPI-APs) from protein folding to transport states. We performed haploid genetic screens to identify factors regulating GPI-inositol deacylation, identifying seven genes. In particular, calnexin cycle impairment caused inefficient GPI-inositol deacylation. Calnexin was specifically associated with GPI-APs, dependent on N-glycan and GPI moieties, and assisted efficient GPI-inositol deacylation by PGAP1. Under chronic ER stress caused by misfolded GPI-APs, inositol-acylated GPI-APs were exposed on the cell surface. These results indicated that N-glycans participate in quality control and temporal ER retention of GPI-APs, ensuring their correct folding and GPI processing before exiting from the ER. Once the system is disrupted by ER stress, unprocessed GPI-APs become exposed on the cell surface.

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