The first step of glycosylphosphatidylinositol biosynthesis is mediated by a complex of PIG-A, PIG-H, PIG-C and GPI1

Reika Watanabe, Norimitsu Inoue, Barbara Westfall, Christopher H. Taron, Peter Orlean, Junji Takeda, Taroh Kinoshita

Research output: Contribution to journalArticlepeer-review

Abstract

Biosynthesis of glycosylphosphatidylinositol (GPI) is initiated by transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to phosphatidylinositol (PI). This chemically simple step is genetically complex because three genes are required in both mammals and yeast. Mammalian PIG-A and PIG-C are homologous to yeast GPI3 and GPI2, respectively; however, mammalian PIG-H is not homologous to yeast GPI1. Here, we report cloning of a human homolog of GPI1 (hGPI1) and demonstrate that four mammalian gene products form a protein complex in the endoplasmic reticulum membrane. PIG-L, which is involved in the second step in GPI synthesis, GlcNAc-PI de-N-acetylation, did not associate with the isolated complex. The protein complex had GPI-GlcNAc transferase (GPI-GnT) activity in vitro, but did not mediate the second reaction, Bovine PI was utilized ~ 100-fold more efficiently than soybean PI as a substrate, and lyse PI was a very inefficient substrate, These results suggest that GPI-GnT recognizes the fatty acyl chains of PI, The unusually complex organization of GPI-GnT may be relevant to selective usage of PI and/or regulation.

Original languageEnglish (US)
Pages (from-to)877-885
Number of pages9
JournalEMBO Journal
Volume17
Issue number4
DOIs
StatePublished - Feb 4 1998

Keywords

  • ER
  • GPI anchor
  • GPI1
  • N-acetylglucosaminyl transferase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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