Skip to main content
Log in

Analysis of biochemical features of ST8 α-N-acetyl-neuraminide α2,8-sialyltransferase (St8sia) 5 isoforms

  • Original Article
  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Gangliosides are important components of the membrane and are involved in many biological activities. St8sia5 is an α2,8-sialyltransferase involved in ganglioside synthesis, and has three isoforms. In this study, we analyzed the features of three isoforms, St8sia5-S, -M, and -L that had not been analyzed, and found that only St8sia5-L was localized in the Golgi, while the majority of St8sia5-M and -S were localized in the ER. The localization of Golgi of St8sia5 depended on the stem region. In addition, the incorporation of exogenous GD3 was upregulated only in St8sia5-L expressing cells. Taken together, the localization of St8sia5 is important for the activity of the enzyme.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Yu, R.K., Tsai, Y.T., Ariga, T., Yanagisawa, M.: Structures, biosynthesis, and functions of gangliosides–an overview. J. Oleo. Sci. 60, 537–544 (2011). https://doi.org/10.5650/jos.60.537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sarmento, M.J., Ricardo, J.C., Amaro, M., Šachl, R.: Organization of gangliosides into membrane nanodomains. FEBS Lett. 594, 3668–3697 (2020). https://doi.org/10.1002/1873-3468.13871

    Article  CAS  PubMed  Google Scholar 

  3. Furukawa, K., Ohmi, Y., Ohkawa, Y., Bhuiyan, R.H., Zhang, P., Tajima, O., Hashimoto, N., Hamamura, K.: New era of research on cancer-associated glycosphingolipids. Cancer Sci 110, 1544–1551 (2019). https://doi.org/10.1111/cas.14005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Furukawa, K., Ohmi, Y., Kondo, Y., Ohkawa, Y., Tajima, O.: Regulatory function of glycosphingolipids in the inflammation and degeneration. Arch. Biochem. Biophys. 571, 58–65 (2015). https://doi.org/10.1016/j.abb.2015.02.007

    Article  CAS  PubMed  Google Scholar 

  5. Furukawa, K., Ohmi, Y., Ohkawa, Y., Tajima, O.: Glycosphingolipids in the regulation of the nervous system. Adv. Neurobiol. 9, 307–320 (2014). https://doi.org/10.1007/978-1-4939-1154-7_14

    Article  PubMed  Google Scholar 

  6. Hakomori, S.: Tumor-associated carbohydrate antigens defining tumor malignancy: basis for development of anti-cancer vaccines. Adv. Exp. Med. Biol. 491, 369–402 (2001)

    Article  CAS  Google Scholar 

  7. Sarkar, T.R., Battula, V.L., Werden, S.J., Vijay, G.V., Ramirez-Peña, E.Q., Taube, J.H., Chang, J.T., Miura, N., Porter, W., Sphyris, N., Andreeff, M., Mani, S.A.: GD3 synthase regulates epithelial-mesenchymal transition and metastasis in breast cancer. Oncogene. 34, 2958–2967 (2015). https://doi.org/10.1038/onc.2014.245

    Article  CAS  PubMed  Google Scholar 

  8. Cazet, A., Julien, S., Bobowski, M., Krzewinski-Recchi, M.A., Harduin-Lepers, A., Groux-Degroote, S., Delannoy, P.: Consequences of the expression of sialylated antigens in breast cancer. Carbohydr. Res. 345, 1377–1383 (2010). https://doi.org/10.1016/j.carres.2010.01.024

    Article  CAS  PubMed  Google Scholar 

  9. Sato, C., Kitajima, K.: Disialic, oligosialic and polysialic acids: distribution, functions and related disease. J. Biochem. 154, 115–136 (2013). https://doi.org/10.1093/jb/mvt057

    Article  CAS  PubMed  Google Scholar 

  10. Kono, M., Yoshida, Y., Kojima, N., Tsuji, S.:Molecular cloning and expression of a fifth type of alpha2,8-sialyltransferase (ST8Sia V). Its substrate specificity is similar to that of SAT-V/III, which synthesize GD1c, GT1a, GQ1b and GT3. J. Biol. Chem. 271, 29366–29371 (1996)

  11. Sasaki, K., Kurata, K., Kojima, N., Kurosawa, N., Ohta, S., Hanai, N., Tsuji, S., Nishi, T.: Expression cloning of a GM3-specific alpha-2,8-sialyltransferase (GD3 synthase). J. Biol. Chem. 269, 15950–15956 (1994)

    Article  CAS  Google Scholar 

  12. Kim, Y.J., Kim, K.S., Do, S., Kim, C.H., Kim, S.K., Lee, Y.C.: Molecular cloning and expression of human alpha2,8-sialyltransferase (hST8Sia V). Biochem. Biophys. Res. Commun. 235, 327–330 (1997). https://doi.org/10.1006/bbrc.1997.6725

    Article  CAS  PubMed  Google Scholar 

  13. Tsuji, S., Takashima, S.: ST8 Alpha-N-Acetyl-Neuraminide Alpha-2,8-Sialyltransferase 5 (ST8SIA5), Springer 14, 813–821 (2014)

  14. Okada, M., Itoh Mi, M., Haraguchi, M., Okajima, T., Inoue, M., Oishi, H., Matsuda, Y., Iwamoto, T., Kawano, T., Fukumoto, S., Miyazaki, H., Furukawa, K., Aizawa, S.: b-series Ganglioside deficiency exhibits no definite changes in the neurogenesis and the sensitivity to Fas-mediated apoptosis but impairs regeneration of the lesioned hypoglossal nerve. J. Biol. Chem. 277, 1633–1636 (2002). https://doi.org/10.1074/jbc.C100395200.

  15. Sugiura, Y., Furukawa, K., Tajima, O., Mii, S., Honda, T.: Sensory nerve-dominant nerve degeneration and remodeling in the mutant mice lacking complex gangliosides. Neuroscience. 135, 1167–1178 (2005). https://doi.org/10.1016/j.neuroscience.2005.07.035

    Article  CAS  PubMed  Google Scholar 

  16. Komura, N., Kato, K., Udagawa, T., Asano, S., Tanaka, H.N., Imamura, A., Ishida, H., Kiso, M., Ando, H.: Constrained sialic acid donors enable selective synthesis of α-glycosides. Science. 364, 677–680 (2019). https://doi.org/10.1126/science.aaw4866

    Article  CAS  PubMed  Google Scholar 

  17. Hane, M., Kitajima, K., Sato, C.: Effects of intronic single nucleotide polymorphisms (iSNPs) of a polysialyltransferase, ST8SIA2 gene found in psychiatric disorders on its gene products. Biochem. Biophys. Res. Commun. 478, 1123–1129 (2016). https://doi.org/10.1016/j.bbrc.2016.08.079

    Article  CAS  PubMed  Google Scholar 

  18. Inoko, E., Nishiura, Y., Tanaka, H., Takahashi, T., Furukawa, K., Kitajima, K., Sato, C.: Developmental stage-dependent expression of an alpha2,8-trisialic acid unit on glycoproteins in mouse brain. Glycobiology. 20, 916–928 (2010) . cwq049[pii]1093/glycob/cwq049

  19. Go, S., Veillon, L., Ciampa, M.G., Mauri, L., Sato, C., Kitajima, K., Prinetti, A., Sonnino, S., Inokuchi, J.I.: Altered expression of ganglioside GM3 molecular species and a potential regulatory role during myoblast differentiation. J. Biol. Chem. 292, 7040–7051 (2017). https://doi.org/10.1074/jbc.M116.771253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Konishi, M., Komura, N., Hirose, Y., Suganuma, Y., Tanaka, H.N., Imamura, A., Ishida, H., Suzuki, K.G.N., Ando, H.: Development of Fluorescent Ganglioside GD3 and GQ1b Analogs for Elucidation of Raft-Associated Interactions. J. Org. Chem. 85, 15998–16013 (2020). https://doi.org/10.1021/acs.joc.0c01493

    Article  CAS  PubMed  Google Scholar 

  21. Takashima, S., Tachida, Y., Nakagawa, T., Hamamoto, T., Tsuji, S.: Quantitative analysis of expression of mouse sialyltransferase genes by competitive PCR. Biochem. Biophys. Res. Commun. 260, 23–27 (1999). S0006–291X(99)90794–5[pii]1006/bbrc.1999.0794

  22. Takashima, S., Ishida, H., Inazu, T., Ando, T., Ishida, H., Kiso, M., Tsuji, S., Tsujimoto, M.: Molecular cloning and expression of a sixth type of alpha 2,8-sialyltransferase (ST8Sia VI) that sialylates O-glycans. J. Biol. Chem. 277, 24030–24038 (2002). M112367200 [pii]1074/jbc.M112367200

  23. Sato, C., Fukuoka, H., Ohta, K., Matsuda, T., Koshino, R., Kobayashi, K., Troy, F., Kitajima, K.: Frequent occurrence of pre-existing alpha 2 -> 8-linked disialic and oligosialic acids with chain lengths up to 7 Sia residues in mammalian brain glycoproteins - Prevalence revealed by highly sensitive chemical methods and anti-di-, oligo-, and poly-Sia antibodies specific for defined chain lengths. J. Biol. Chem. 275, 15422–15431 (2000). https://doi.org/10.1074/jbc.275.20.15422

    Article  CAS  PubMed  Google Scholar 

  24. Anastasia, L., Holguera, J., Bianchi, A., D’Avila, F., Papini, N., Tringali, C., Monti, E., Villar, E., Venerando, B., Muñoz-Barroso, I., Tettamanti, G.: Over-expression of mammalian sialidase NEU3 reduces Newcastle disease virus entry and propagation in COS7 cells. Biochim. Biophys. Acta. 1780, 504–512 (2008). https://doi.org/10.1016/j.bbagen.2007.11.011

    Article  CAS  PubMed  Google Scholar 

  25. Johswich, A., Kraft, B., Wuhrer, M., Berger, M., Deelder, A.M., Hokke, C.H., Gerardy-Schahn, R., Bakker, H.: Golgi targeting of Drosophila melanogaster beta4GalNAcTB requires a DHHC protein family-related protein as a pilot. J. Cell. Biol. 184, 173–183 (2009). https://doi.org/10.1083/jcb.200801071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tu, L., Tai, W.C., Chen, L., Banfield, D.K.: Signal-mediated dynamic retention of glycosyltransferases in the Golgi. Science. 321, 404–407 (2008). https://doi.org/10.1126/science.1159411

    Article  CAS  PubMed  Google Scholar 

  27. Uemura, S., Yoshida, S., Shishido, F., Inokuchi, J.: The cytoplasmic tail of GM3 synthase defines its subcellular localization, stability, and in vivo activity. Mol. Biol. Cell. 20, 3088–3100 (2009). https://doi.org/10.1091/mbc.e08-12-1219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Uemura, S., Shishido, F., Kashimura, M., Inokuchi, J.: The regulation of ER export and Golgi retention of ST3Gal5 (GM3/GM4 synthase) and B4GalNAcT1 (GM2/GD2/GA2 synthase) by arginine/lysine-based motif adjacent to the transmembrane domain. Glycobiology. 25, 1410–1422 (2015). https://doi.org/10.1093/glycob/cwv071

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported in part by Grants-in-Aid for Scientific Research B (21H02425) and AMED (20ae0101069h0005) to CS and Grant-in-Aid for JSPS Fellows (EA). RH was supported by the Nagoya University CIBoG program from the MEXT WISE program.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chihiro Sato.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article belongs to the Topical Collection: Tribute to Professor Sen-itiroh Hakomori

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Araki, E., Hane, M., Hatanaka, R. et al. Analysis of biochemical features of ST8 α-N-acetyl-neuraminide α2,8-sialyltransferase (St8sia) 5 isoforms. Glycoconj J 39, 291–302 (2022). https://doi.org/10.1007/s10719-021-10034-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-021-10034-8

Keywords

Navigation