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Chief Scientist Laboratories Glycometabolic Biochemistry Laboratory

Chief Scientist: Tadashi Suzuki (D.Sc.)

Research Summary

Tadashi  Suzuki

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 largely 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, and also taking a number of approaches to analyze the physiological importance of this non-lysosomal metabolic pathway.

Main Research Fields

  • Biological Sciences

Related Research Fields

  • Biology
  • Medicine, Dentistry & Pharmacy

Keywords

  • glycoproteins
  • Asparagine-linked glycans
  • metabolism
  • Peptide:N-glycanase
  • NGLY1

Selected Publications

  • 1. Yoshida, Y., Asahina, M., Murakami, A., Kawasaki, J., Yoshida, M., Fujinawa, R., Iwai, K., Tozawa, R., Matsuda, N., Tanaka, K., and Suzuki, T.
    "Loss of peptide:N-glycanase causes proteasome dysfunction mediated by a sugar-recognizing ubiquitin ligase"
    Proc. Natl. Acad. Sci. USA 118, e2102902118 (2021)
  • 2. Asahina, M., Fujinawa, R., Hirayama, H., Tozawa, R., Kajii, Y., and Suzuki, T.
    "Reversibility of motor dysfunction in the rat model of NGLY1 deficiency"
    Mol. Brain, 14, 91 (2021)
  • 3. Hosomi, A., Iida, K., Cho, T., Iida, K., Kaneko, M., and Suzuki, T.
    "The ER-associated protease Ste24 prevents N-terminal signal peptide-independent translocation into the endoplasmic reticulum in Saccharomyces cerevisiae"
    J. Biol. Chem. 295, 10406-10419 (2020)
  • 4. Asahina, M., Fujinawa, R.,Nakamura, S., Yokoyama, K., Tozawa, R., and Suzuki, T.
    "Ngly1-/- rats develop neurodegenerative phenotypes and pathological abnormalities in their peripheral and central nervous systems"
    Hum Mol. Genet. 29, 1635-1647 (2020)
  • 5. Fujihira, H., Masahara-Negishi, Y., Akimoto, Y., Hirayama, H., Lee, H.-C., Story, B. A., Mueller, W. F., Jakob, P., Clauder-Munster, S., Sterinmetz, L. M., Radhakrishnan, S. K., Kawakami, H., Kamada, Y., Miyoshi, E., Yokomizo, T. and Suzuki, T.
    "Liver-specific deletion of Ngly1 causes abnormal nuclear morphology and lipid metabolism under food stress"
    Biochim. Biophys. Acta Mol. Basis Dis. 1866, 165588 (2020)
  • 6. Hirayama, H., Matsuda, T., Tsuchiya, Y., Oka, R., Seino, J., Huang, C., Nakajima, K., Noda, Y., Shichino, Y., Iwasaki, S., and Suzuki, T.
    "Free glycans derived from O-mannosylated glycoproteins suggest the presence of an O-glycoprotein degradation pathway in yeast"
    J. Biol. Chem. 294, 15900-15911 (2019)*selected as "Editors' pick"
  • 7. 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)
  • 8. 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, 8048-8058 (2016)
  • 9. 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)
  • 10. 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)

Annual research report

Related Links

Lab Members

Principal investigator

Tadashi Suzuki
Chief Scientist

Core members

Masashi Ueki
Senior Research Scientist
Ken-ichi Moto
Senior Research Scientist
Katsuhiko Kamada
Senior Research Scientist
Hiroto Hirayama
Research Scientist
Haruhiko Fujihira
Research Scientist
Yuriko Tachida
Technical Scientist
Akinobu Honda
Special Postdoctoral Researcher
Chengcheng Huang
Postdoctoral Researcher
Shengtao Li
Postdoctoral Researcher
Stuart James Emmerson
Postdoctoral Researcher
Ryosuke Koyama
Postdoctoral Researcher
Keiko Sato
Technical Staff I
Reiko Fujinawa
Technical Staff I
Junichi Seino
Technical Staff I
Shino Manabe
Visiting Scientist
Yoichi Takeda
Visiting Scientist
Yuko Suzuki
Assistant
Tsugiyo Matsuda
Research Part-time Worker II
Akemi Suzuki
Research Part-time Worker II

Contact Information

S405 Bioscience Bldg,
2-1 Hirosawa, Wako, Saitama 351-0198, Japan
Email: tsuzuki_gm [at] riken.jp

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