Glycosylphosphatidylinositol-N-Acetylglucosaminyltransferase (GPI-GlcNAc Transferase): A Complex Comprised of PIGA, PIGC, PIGH, PIGQ, PIGP, PIGY and DPM2

  • Taroh Kinoshita
  • Norimitsu Inoue
  • Yoshiko Murakami
Reference work entry


Glycosylphosphatidylinositols (GPIs) function as an anchor linking cell surface proteins to the plasma membrane in a wide range of eukaryotic organisms from yeast to mammals (Ferguson et al. 2009; Orlean and Menon 2007). In mammalian cells, many kinds of GPI-anchored proteins (GPI-APs) with various functions have been identified, including enzymes, ligands, receptors, adhesion molecules, complement regulators, and other immunological proteins (Ferguson et al. 2009). GPI-AP precursors possess a GPI-anchor attachment signal at the carboxyl-terminus. The GPI signal sequence is cleaved and replaced by a GPI preassembled in the endoplasmic reticulum (ER). The transfer of this GPI to proteins is essential for their expression on the cell surface. The core structure of GPIs is conserved in most eukaryotic organisms and is comprised of EtNP-6Manα1-2Manα1-6Manα1-4GlcNα1-6myo-Inositol-phospholipid (EtNP, ethanolamine phosphate; Man, mannose; GlcN, glucosamine) (Fig. 106.1a). The EtNP of the GPI core is amide-bonded to the carboxyl-terminus of GPI-APs. During GPI-anchor biosynthesis before transfer to the protein, the GPI core is additionally modified by a palmitate (or myristate in some cases) linked to the second position of the inositol moiety, with the EtNP side branches linked to the second position of the first mannose and the sixth position of the second mannose and with the fourth mannose linked to the third mannose via an a1-2 bond (Fig. 106.1a) (Kinoshita et al. 2008; Maeda and Kinoshita 2011). In mammalian nucleated cells, the palmitate chain of the inositol moiety is generally removed in the ER soon after the transfer of GPI to the protein (Tanaka et al. 2004). The first and second mannoses of the GPI core are also occasionally modified with various side branch sugars in the Golgi. In mammals, most free phosphatidylinositols (PIs) have diacyl fatty chains containing an unsaturated fatty acid at the sn2 position (primarily C18:0-C20:4), whereas the GPI-APs on the plasma membrane predominantly possess unique 1-alkyl-2-acyl fatty chains containing a saturated fatty acyl chain (usually stearic acid) at the sn2 position. The conversion of diacyl chains to 1-alkyl-2-acyl fatty chains occurs during GPI-anchor biosynthesis in the ER using an alkyl donor derived from the peroxisome (Maeda and Kinoshita 2011). The unsaturated fatty acyl chain at the sn-2 position is then remodeled to stearic acid by PGAP3 and PGAP2 in the Golgi (Maeda et al. 2007; Tashima et al. 2006).


Down Syndrome Paroxysmal Nocturnal Hemoglobinuria Paroxysmal Nocturnal Hemoglobinuria Patient Ethanolamine Phosphate Unsaturated Fatty Acyl Chain 
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Copyright information

© Springer Japan 2014

Authors and Affiliations

  • Taroh Kinoshita
    • 1
  • Norimitsu Inoue
    • 2
  • Yoshiko Murakami
    • 1
  1. 1.Department of Immunoregulation, Research Institute for Microbial DiseasesOsaka UniversitySuitaJapan
  2. 2.Department of Molecular GeneticsOsaka Medical Center for Cancer and Cardiovascular DiseasesOsakaJapan

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