Kinoshita Lab/Endowed Chair  Yabumoto Department of Intractable Disease Research

Glycosylphosphatidylinositol (GPI) is a glycolipid attached to proteins and anchors them onto the plasma membrane. GPI-anchored protein has various and important physiological functions in our body. Why proteins have this peculiar structure like GPI? Our research goal is to elucidate biogenesis, transport and remodeling of GPI-anchored proteins and understand its physiological significance in our body.

How are GPI-anchored proteins (GPI-APs) regulated?

GPI anchors are synthesized in the endoplasmic reticulum and attached to the C terminus of proteins during posttranslational modification. GPI-anchored proteins are transported from the endoplasmic reticulum to the Golgi and further to the cell surface in a way that is regulated according to the features of GPI. Recently, we identified the enzyme that can cut GPI-anchors, and showed GPI-APs can be secreted and work in the tissues distant from its origin. This result indicates that GPI anchors enable our body system to regulate where and when the protein works in a various way. We are currently studying the molecular mechanism to control the functions of GPI-APs. In addition, GPI anchor has specific carbohydrate side-chains and intriguingly, the chain varies among cells and proteins. We are interested in the physiological significance of this carbohydrate chain and asking how this chain is synthesized in our cells.

Molecular mechanisms of GPI deficiencies.

We found that paroxysmal nocturnal hemoglobinuria (PNH) is caused by somatic mutation of the X-linked PIGA gene, a gene for GPI-anchor biosynthesis. A recent report showed that atypical PNH is caused by somatic mutation of one allele of the PIGT gene, a gene for GPI-anchor attachment, in combination with a germline mutation in the other allele. Now, we are studying how unused GPI-anchor is involved in pathogenesis of atypical PNH and try to find a cure for this disease.

We also identified a disease called inherited GPI deficiency (IGD) caused by the mutation of the GPI-anchor synthesizing enzyme, PIGM. The recent whole exome sequencing analysis using the next generation sequencer revealed 16 GPI-related gene mutations responsible for IGD. To elucidate the molecular mechanisms of the pathogenesis of this disease, we developed the system to analyze GPI biosynthesis and modification. This system contributes to the IGD research in all over the world. Our aim is to elucidate how GPI-anchors are involved in IGD and find the way to overcome this disease.

  • GPI-anchor biosynthesis and the transport/remodeling of GPI-APs.


  • Endowed Chair Prof.: Taroh Kinoshita
  • Endowed Chair Prof.: Yoshiko Murakami
  • Postdoc.: WANG YICHENG



  • (1) Identification of a Golgi GPI-N-acetylgalactosamine transferase with tandem transmembrane regions in the catalytic domain. Hirata, T., et al. Nat. Commun. (2018) 9:405.
    (2) N-Glycan dependent protein folding and endoplasmic reticulum retention regulate GPI-anchor processing. Liu, Y.-S., et al. J. Cell Biol. (2017) 217: 585-599.
    (3) Phenotype-genotype correlations of PIGO deficiency with variable phenotypes from infantile lethality to mild learning difficulties. Tanigawa, J., et al. Hum. Mutat. (2017) 38:805-815.
    (4) A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in embryos by shedding CRIPTO. Lee, G-H., et al. J. Cell Biol. (2016) 215:705-718.
    (5) Pathogenic variants in PIGG cause intellectual disability with seizures and hypotonia. Makrythanasis, P., et al. Am. J. Hum. Genet. (2016) 98:615-626.
    (6) Post-Golgi anterograde transport requires GARP-dependent endosome-to-TGN retrograde transport. Hirata, T., et al. Mol. Biol. Cell (2015) 26:3071-3084.