Initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-P and is regulated by DPM2

EMBO J. 2000 Aug 15;19(16):4402-11. doi: 10.1093/emboj/19.16.4402.


Glycosylphosphatidylinositols (GPIs) are attached to the C-termini of many proteins, thereby acting as membrane anchors. Biosynthesis of GPI is initiated by GPI-N-acetylglucosaminyltransferase (GPI-GnT), which transfers N-acetylglucosamine from UDP- N-acetylglucosamine to phosphatidylinositol. GPI-GnT is a uniquely complex glycosyltransferase, consisting of at least four proteins, PIG-A, PIG-H, PIG-C and GPI1. Here, we report that GPI-GnT requires another component, termed PIG-P, and that DPM2, which regulates dolichol-phosphate-mannose synthase, also regulates GPI-GnT. PIG-P, a 134-amino acid protein having two hydrophobic domains, associates with PIG-A and GPI1. PIG-P is essential for GPI-GnT since a cell lacking PIG-P is GPI-anchor negative. DPM2, but not two other components of dolichol-phosphate-mannose synthase, associates with GPI-GnT through interactions with PIG-A, PIG-C and GPI1. Lec15 cell, a null mutant of DPM2, synthesizes early GPI intermediates, indicating that DPM2 is not essential for GPI-GnT; however, the enzyme activity is enhanced 3-fold in the presence of DPM2. These results reveal new essential and regulatory components of GPI-GnT and imply co-regulation of GPI-GnT and the dolichol-phosphate-mannose synthase that generates a mannosyl donor for GPI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD59 Antigens / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cell Separation
  • Cloning, Molecular
  • DNA, Complementary / metabolism
  • Dolichol Monophosphate Mannose / metabolism
  • Expressed Sequence Tags
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Fungal Proteins / chemistry
  • Glycosylphosphatidylinositols / biosynthesis*
  • Glycosylphosphatidylinositols / genetics
  • Hexosyltransferases
  • Humans
  • Mannosyltransferases*
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • N-Acetylglucosaminyltransferases / chemistry
  • N-Acetylglucosaminyltransferases / metabolism
  • Plant Proteins / chemistry
  • Plasmids / metabolism
  • Protein Binding
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Transfection


  • CD59 Antigens
  • Carrier Proteins
  • DNA, Complementary
  • Dscr5 protein, mouse
  • Fungal Proteins
  • Glycosylphosphatidylinositols
  • Membrane Proteins
  • PIGH protein, human
  • Plant Proteins
  • phosphatidylinositol glycan-class A protein
  • Dolichol Monophosphate Mannose
  • DPM2 protein, human
  • Hexosyltransferases
  • Mannosyltransferases
  • N-Acetylglucosaminyltransferases
  • N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase
  • PIGC protein, human
  • PIGP protein, human