2. Academic Validation
  3. Accumulated precursors of specific GPI-anchored proteins upregulate GPI biosynthesis with ARV1

Accumulated precursors of specific GPI-anchored proteins upregulate GPI biosynthesis with ARV1

  • J Cell Biol. 2023 May 1;222(5):e202208159. doi: 10.1083/jcb.202208159.
Yi-Shi Liu # 1,  Yicheng Wang # 2 3,  Xiaoman Zhou 1,  Linpei Zhang 1,  Ganglong Yang 1,  Xiao-Dong Gao 1,  Yoshiko Murakami 2 3,  Morihisa Fujita 1 4,  Taroh Kinoshita 2 3 5
Affiliations

Affiliations

  • 1 Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University , Wuxi, China.
  • 2 Research Institute for Microbial Diseases, Osaka University , Suita, Japan.
  • 3 WPI Immunology Frontier Research Center, Osaka University , Suita, Japan.
  • 4 Institute for Glyco-Core Research, Gifu University , Gifu, Japan.
  • 5 Center for Infectious Disease Education and Research, Osaka University , Suita, Japan.
  • # Contributed equally.
PMID: 36828365 DOI: 10.1083/jcb.202208159
Abstract

We previously reported that glycosylphosphatidylinositol (GPI) biosynthesis is upregulated when endoplasmic reticulum-associated degradation (ERAD) is defective; however, the underlying mechanistic basis remains unclear. Based on a genome-wide CRISPR-Cas9 screen, we show that a widely expressed GPI-anchored protein CD55 precursor and ER-resident ARV1 are involved in upregulation of GPI biosynthesis under ERAD-deficient conditions. In cells defective in GPI transamidase, GPI-anchored protein precursors fail to obtain GPI, with the remaining uncleaved GPI-attachment signal at the C-termini. We show that ERAD deficiency causes accumulation of the CD55 precursor, which in turn upregulates GPI biosynthesis, where the GPI-attachment signal peptide is the active element. Among the 31 GPI-anchored proteins tested, only the GPI-attachment signal Peptides of CD55, CD48, and PLET1 enhance GPI biosynthesis. ARV1 is prerequisite for the GPI upregulation by CD55 precursor. Our data indicate that GPI biosynthesis is balanced to need by ARV1 and precursors of specific GPI-anchored proteins.

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