Identification and characterization of organelle zones for specific glycosylation modifications

Research abstract

It has been estimated that more than half of proteins in nature are modified with glycans. Glycans increase the solubility and stability of proteins as well as keep the structural integrity of protein functional sites and is also actively associated with various biological systems. Glycosylation was not thought to be tightly regulated because the modification is indirectly encoded in genomes. While, we have found some glycosylations are strictly controlled to modify the specific career proteins. Such strict modification seems to be achieved by rigorous substrate specificities of modification enzymes. In addition, it is currently proposed that accessibility of enzymes to their carrier proteins may be tightly regulated by special separation of modification reactions, which are occurred in specific organelle zones.  In this study, we will investigate identification and characterization of the functional zones for specific glycosylation on specific glycoproteins.
In addition, we will contribute to this academic field by facilitating glycosylation analysis using mass spectrometric and HPLC mapping methods.

Original papers

1. Yagi, H., Yagi-Utsumi, M., Honda, R., Ohta, Y., Saito, T., Nishio, M., Ninagawa, S., Suzuki, K., Anzai, T., Kamiya, Y., Aoki, K., Nakanishi, M., Satoh, T. and Kato, K. (2020) Improved secretion of glycoproteins using an N-glycan-restricted passport sequence tag recognized by cargo receptor. Nature Commun., 11, Article number: 1368
2. George, G., Ninagawa, S., Yagi, H., Saito, T., Ishikawa, T., Sakuma, T., Yamamoto, T., Imami, K., Ishihama, Y., Kato, K., Okada, T. and Mori, K. (2020) EDEM2 stably disulfide-bonded to TXNDC11 catalyzes the first mannose trimming step in mammalian glycoprotein ERAD. eLife, 9, e53455
3. Yagi, H., Takakura, D., Roumenina, L.T., Fridman, W.H., Sautès-Fridman, C., Kawasaki, N. and Kato, K. (2018) Site-specific N-glycosylation analysis of soluble Fcγ receptor IIIb in human serum. Sci. Rep., 8, Article number: 2719
4. Yagi, H., Yan, G., Suzuki, T., Tsuge, S., Yamaguchi, T. and Kato, K. Lewis X-carrying neoglycolipids evoke selective apoptosis in neural stem cells (2018) Neurochem. Res., 43, 212-218
5. Yanaka, S., Yamazaki, T., Yogo, R., Noda, M., Uchiyama, S., Yagi, H., and Kato, K. (2017) NMR Detection of Semi-Specific Antibody Interactions in Serum Environments. Molecules 22, E1619
6.  Yogo, R., Yanaka, S., Yagi, H., Martel, A., Porcar, L., Ueki, Y., Inoue, R., Sato, N., Sugiyama, M., and Kato, K. (2007) Characterization of conformational deformation-coupled interaction between immunoglobulin G1 Fc glycoprotein and a low-affinity Fcγ receptor by deuteration-assisted small-angle neutron scattering.　Biochem Biophys Rep 16, 1-4
7. Sawaguchi, S., Varshney, S., Ogawa, M., Sakaidani, Y., Yagi, H., Takeshita, K., Murohara, T., Kato, K., Sundaram, S., Stanley, P., and Okajima, T. (2017) O-GlcNAc on NOTCH1 EGF repeats regulates ligand-induced Notch signaling and vascular development in mammals. Elife 6
8. Yagi, H., Kuo, C. W., Obayashi, T., Ninagawa, S., Khoo, K. H., and Kato, K. (2016) Direct Mapping of Additional Modifications on Phosphorylated O-glycans of alpha-Dystroglycan by Mass Spectrometry Analysis in Conjunction with Knocking Out of Causative Genes for Dystroglycanopathy. Mol Cell Proteomics 15, 3424-3434
9. Nakagawa, N., Yagi, H., Kato, K., Takematsu, H., and Oka, S. (2015) Ectopic clustering of Cajal-Retzius and subplate cells is an initial pathological feature in Pomgnt2-knockout mice, a model of dystroglycanopathy. Sci Rep 5, 11163
10. Yagi, H., Nakagawa, N., Saito, T., Kiyonari, H., Abe, T., Toda, T., Wu, S. W., Khoo, K. H., Oka, S., and Kato, K. (2013) AGO61-dependent GlcNAc modification primes the formation of functional glycans on alpha-dystroglycan. Sci Rep 3, 3288
11. Yagi, H., Saito, T., Yanagisawa, M., Yu, R. K., and Kato, K. (2012) Lewis X-carrying N-glycans regulate the proliferation of mouse embryonic neural stem cells via the Notch signaling pathway. J Biol Chem 287, 24356-24364

Reviews

1. Yamaguchi, Y., Yagi, H., and Kato, K. (2017) Stable isotope labeling of glycoproteins for NMR study. NMR in Glycoscience and Glycotechnology, (K.Kato and T.Peters ed.), RSC Publishing (Cambridge), 194-207
2. Yagi, H. (2017) Development and Application of Glycosylation-Profiling Techniques for Functional Glycomics in the Nervous System. Trends in Glycoscience and Glycotechnology, 29(165), E19-E25, 3.
3. Yagi, H. and Kato, K. (2016) Functional roles of glycoconjugates in the maintenance of stemness and differentiation process of neural stem cells. Glycoconj J, in press, doi:10.1007/s10719-016-9707-x