Glycometabolome Team

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

Research Subjects

• Mechanism of free N-glycan catabolic pathway
• Functional role of cytoplasmic PNGase in ERAD
• Evolutional Diversion of the function of cytoplasmic PNGase

Publications

1. 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)
2. Masahara-Negishi, Y.*., and Hosomi, A.*., Della Mea, M., Serafini-Fracassini, D., and Suzuki, T.:
   "A plant peptide:N-glycanase orthologue facilitates glycoprotein ER-associated degradation in yeast. "
   Biiochim. Biophys. Acta 1820, 1457-1462 (2012) (*: equally contributed)
3. Ishii, K., Saitoh, T., Osada, H., Taniguchi, N. and Suzuki, T.:
   "Identification of compounds that augment the lectin-sensitivity of Chinese Hamster Ovary cells."
   Biochem. Biophys. Res. Commun. 423, 429-435 (2012)
4. Haga, Y., Ishii, K., and Suzuki, T.:
   "N-glycan is essential for stability and intracellular trafficking of glucose transporter, GLUT4."
   J. Biol. Chem. 286, 31320-31327 (2011)
5. Hirayama, H., and Suzuki, T.:
   "Metabolism of free oligosaccharides is facilitated in the och1 mutant of Saccharomyces cerevisiae."
   Glycobiology 21, 1341-1348 (2011)
6. Kato, A.*, Wang, L.*., Ishii, K., Seino, J., Asano, N., and Suzuki, T.:
   "Calystegine B3 as a specific inhibitor for cytoplasmic alpha-mannosidase, Man2C1."
   J. Biochem. 149, 415-422 (2011) (*: equally contributed)
7. 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)
8. Funakoshi, Y., Negishi, Y., Gergen, J. P., Seino, J., Ishii, K., Lennarz, W.J., Matsuo, I., Ito, Y., Taniguchi, N., and Suzuki, T.:
   "Evidence for an essential deglycosylation-independent activity of PNGase in Drosophila melanogaster."
   PLoS One, 5, e10545 (2010)
9. 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)
10. Maerz, S., Funakoshi, Y., Negishi, Y., Suzuki, T., and Seiler, S.:
    "The Neurospora peptide:N-glycanase ortholog PNG1 is essential for cell polarity despite its lack of enzymatic activity."
    J. Biol. Chem. 285, 2326-2332 (2010)