Centers & Labs

Global Research Cluster

Glycometabolome Team

Team Leader: Tadashi Suzuki (D.Sci.)
Tadashi  Suzuki(D.Sci.)

Peptide:N-glycanase (PNGase) releases N-glycans from glycoproteins/glycopeptides. The cytoplasmic PNGases, ubiquitously found throughout eukaryotes, are now widely recognized as a component implicated in the ERAD (ER-associated degradation) process, which constitute one of the quality control machineries for newly synthesized misfolded glycoproteins exported out of the ER lumen. While the biosynthetic pathway for N-glycans has been clarified in detail, the catabolic pathway for the "free" N-glycans released by the cytoplasmic PNGase remains largrely unknown. Although this "non-lysosomal" metabolic path for N-glycan may represent one of the very basic biological phenomena in eukaryotes, there are still many more enzymes/transporters that remains to be identified.. We are currently trying to identify other players involved in this process through collaboration with Max Planck Institute, and also taking a number of approaches to analyze the physiological importance of this non-lysosomal metabolic pathway.

Main Research Field

Biological Sciences

Related Research Fields

Biology / Medicine, dentistry, and pharmacy

Keywords

  • glycoproteins
  • metabolism
  • Ngly1

Selected Publications

  1. Fujihira, H., Masahara-Negishi, Y., Tamura, M., Huang, C., Harada, Y., Wakana, S., Takakura, D., Kawasaki, N., Taniguchi, N., Kondoh, G., Yamashita, T., Funakoshi, Y., and Suzuki, T.
    "Lethality of Ngly1-knockout mice is partially rescued by the additional deletion of the Engase gene."
    PLOS Genet. 13, e1006696 (2017)
  2. Harada, Y. Huang, C., Yamaki, S., Dohmae, N., and Suzuki, T.:
    "Non-lysosomal degradation of phophorylated oligosaccharides is initiated by the cytosolic endo-β-N-acetylglucosaminidase."
    J. Biol. Chem. 291, 291, 8048-8058 (2016)
  3. Huang, C., Harada, Y., Hosomi, A., Masahara-Negishi, Y., Seino, J., Fujihira, H., Funakoshi, Y., Suzuki, T., Dohmae, N., and Suzuki, T.:
    "Endo-β-N-acetylglucosaminidase forms N-GlcNAc protein aggregates during ER-associated degradation in Ngly1-defective cells."
    Proc. Natl. Acad. Sci. USA 112, 1398-1403 (2015)
  4. Harada, Y., Nakajima, K., Masahara-Negishi, Y., Freeze, H. H., Angata, T., Taniguchi, N., and Suzuki, T.:
    "Metabolically programmed quality control system for dolichol-linked oligosaccharides."
    Proc. Natl. Acad. Sci. USA 110, 19366-19371 (2013)
  5. Harada, Y., Buser, R., Ngwa, E. M., Hirayama, H., Aebi, M., and Suzuki, T.:
    "Eukaryotic oligosaccharyltransferase generates free oligosaccharides during N-glycosylation."
    J. Biol. Chem. 288, 32673-32684 (2013)
  6. Seino, J., Wang, L., Harada, Y., Huang, C., Ishii, K., Mizushima, N., and Suzuki, T.:
    "Basal autophagy is required for the efficient catabolism of sialyl oligosaccharides."
    J. Biol. Chem. 288, 26898-26907 (2013)
  7. Wang, L., and Suzuki, T.:
    "Dual functions for cytosolic alpha-mannosidase (Man2C1): its downregulation causes mitochondria-dependent apotosis independently of it's alpha-mannosidase activity."
    J. Biol. Chem. 288, 11887-11896 (2013)
  8. Haga, Y., Ishii, K., Hibino, K., Sako, Y., Ito, Y., Taniguchi, N., and Suzuki, T.:
    "Visualizing specific protein glycoforms by transmembrane fluorescence energy transfer."
    Nature Communications 3, 907 (2012)
  9. Hosomi, A., Tanabe, K., Hirayama, H., Kim, I., Rao, H., and Suzuki, T.:
    "Identification of an Htm1 (EDEM)-dependent, Mns1-independent endoplasmic reticulum-associated degradation (ERAD) pathway in Saccharomyces cerevisiae. Application of a novel assay for glycoprotein ERAD."
    J. Biol. Chem. 285, 24324-24334 (2010)
  10. Hirayama, H., Seino, J., Kitajima, T., Jigami, Y., and Suzuki, T.:
    "Free oligosaccharides to monitor glycoprotein endoplasmic reticulum-associated degradation in Saccharomyces cerevisiae."
    J. Biol. Chem. 285, 12390-12404 (2010)

Lab Members

Principal Investigator

Tadashi Suzuki
Team Leader

Core Members

Chengcheng Huang
Foreign Postdoctoral Researcher
Junichi Seino
Technical Staff I
Hiroto Hirayama
Visiting Scientist
Haruhiko Fujihira
Visiting Scientist
Kotoko Ueno
Part-timer 2
Yae Tsuchiya
Part-timer 2
Tsugiyo Matsuda
Part-timer 2

Contact information

2-1 Hirosawa, Wako, Saitama 351-0198, Japan

Email: tsuzuki_gm [at] riken.jp

Recent research results