Chief Scientist Laboratories Glycometabolic Biochemistry Laboratory
Chief Scientist: Tadashi Suzuki (D.Sc.)
Research Summary
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
- Chengcheng Huang
- Postdoctoral Researcher
- Shengtao Li
- Postdoctoral Researcher
- Stuart James Emmerson
- Postdoctoral Researcher
- Ryosuke Koyama
- Postdoctoral Researcher
- Akinobu Honda
- Postdoctoral Researcher
- Fuka Onoue
- Student Trainee
- 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
- Ritsuko Oka
- Research Part-time Worker II
- Tsugiyo Matsuda
- Research Part-time Worker II
Contact Information
S405 Bioscience Bldg,
2-1 Hirosawa, Wako, Saitama 351-0198, Japan
Email: tsuzuki_gm [at] riken.jp