Skip to main content
SpringerLink
Log in

GM1 structural requirements to mediate neuronal functions

  • Research
  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Since the 1980s, it has been known that the administration of ganglioside GM1 to cultured cells induced or enhanced neuronal differentiation. GM1 mechanism of action relies on its direct interaction and subsequent activation of the membrane tyrosine kinase receptor, TrkA, which naturally serves as NGF receptor. This process is mediated by the sole oligosaccharide portion of GM1, the pentasaccharide β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal-(1-4)-β-Glc. Here we detailed the minimum structural requirements of the oligosaccharide portion of GM1 for mediating the TrkA dependent neuritogenic processing. By in vitro and in silico biochemical approaches, we demonstrated that the minimal portion of GM1 required for the TrkA activation is the inner core of the ganglioside’s oligosaccharide β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal. The addition of a sialic acid residue at position 3 of the outer galactose of the GM1 oligosaccharide, which forms the oligosaccharide of GD1a, prevented the interaction with TrkA and the resulting neuritogenesis. On the contrary, the addition of a fucose residue at position 2 of the outer galactose, forming the Fucosyl-GM1 oligosaccharide, did not prevent the TrkA-mediated neuritogenesis.

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

Access this article

Log in via an institution

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

Data availability statement

The data presented in this study are available upon reasonable request to the corresponding author.

Abbreviations

Asialo-GM1:

Gg4Cer, β-Gal-(1-3)-β-GalNAc-(1-4)-β-Gal-(1-4)-β-Glc-(1-1)-Cer

Asialo-OligoGM1:

Gg4, β-Gal-(1-3)-β-GalNAc-(1-4)-β-Gal-(1-4)-Glc

BSA:

Bovine serum albumin

CTRL:

Control

DMEM:

Dulbecco’s modified Eagle’s medium

DTT:

1,4-Dithiothreitol

ESI:

Electrospray ionization process

FBS:

Fetal bovine serum

Fuc-OligoGM1:

Fucosyl-GM1 oligosaccharide, IV2αFucII3Neu5Ac-Gg4, α-Fuc-(1-2)-β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal-(1-4)-Glc

Fuc-GM1:

Fucosyl-GM1, Fucosyl-GM1IV2αFucII3Neu5AcGg4Cer, α-Fuc-(1-2)-β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal-(1-4)-β-Glc-(1-1)-Cer

GM1:

II3Neu5Ac-Gg4Cer, β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal-(1-4)-β-Glc-(1-1)-Cer

GM2:

II3Neu5Ac-Gg3Cer, β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal-(1-4)-β-Glc-(1-1)-Cer

GM3:

II3Neu5Ac-Lac-Cer, α-Neu5Ac-(2-3)-β-Gal-(1-4)-β-Glc-(1-1)-Cer

GD1a:

IV3Ne5AcII3Neu5Ac-Gg4Cer, α-Neu5Ac-(2-3)-β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal-(1-4)-β-Glc-(1-1)-Cer

HPTLC:

High-performance thin-layer chromatography

MAPK:

Mitogen-activated protein kinase

MS:

Mass spectrometry

N2a:

Neuroblastoma Neuro2a cells

NGF:

Nerve growth factor

NMR:

Nuclear magnetic resonance

OligoGM1:

GM1 oligosaccharide, II3Neu5Ac-Gg4, β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal-(1-4)-Glc

OligoGD1a:

GD1a oligosaccharide, IV3Ne5AcII3Neu5Ac-Gg4

OligoGM3:

GM3 oligosaccharide, II3Neu5Ac-Lac, α-Neu5Ac-(2-3)-β-Gal-(1-4)-Glc

OligoGM2:

GM2 oligosaccharide, II3Neu5Ac-Gg3, β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal-(1-4)-Glc

OligoGM1 w/o Glc:

GM1 oligosaccharide without glucose; β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-Gal

P/S:

Penicillin/streptomycin

pTrk:

Phosphorylated Trk

PVDF:

Polyvinylidene difluoride

reduced-OligoGM1:

GM1 oligosaccharide containing reduced glucose in position 1, β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal-(1-4)-Glucitol

TBS-T:

Tris-buffered saline containing 0.1% Tween-20

Tyr:

Tyrosine

Trk:

Neurotrophin tyrosin kinase receptor

w/o:

Without

WT:

Wild-type

References

  1. Chester, M.A.: IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature of glycolipids–recommendations 1997. Eur. J. Biochem. 257, 293–298 (1998)

    Article  PubMed  CAS  Google Scholar 

  2. Svennerholm, L.: Composition of gangliosides from human brain. Nature 177, 524–525 (1956)

    Article  PubMed  Google Scholar 

  3. Sonnino, S., Brocca, P., Acquotti, D., Bernardi, A., Raimondi, L., Kiso, M., Ishida, H., Li, S.C., Li, Y.T.: The structural basis for the susceptibility of gangliosides to enzymatic degradation. Biosci. Rep. 19, 163–168 (1999)

    Article  PubMed  CAS  Google Scholar 

  4. Sonnino, S., Aureli, M., Grassi, S., Mauri, L., Prioni, S., Prinetti, A.: Lipid rafts in neurodegeneration and neuroprotection. Mol. Neurobiol. 50, 130–148 (2014)

    Article  PubMed  CAS  Google Scholar 

  5. Chiricozzi, E.: Plasma membrane glycosphingolipid signaling: a turning point. Glycoconj. J. 39, 99–105 (2022)

    Article  PubMed  CAS  Google Scholar 

  6. Sarmento, M.J., Ricardo, J.C., Amaro, M., Šachl, R.: Organization of gangliosides into membrane nanodomains. FEBS Lett. 594, 3668–3697 (2020)

    Article  PubMed  CAS  Google Scholar 

  7. Ledeen, R.W., Wu, G.: The multi-tasked life of GM1 ganglioside, a true factotum of nature. Trends Biochem. Sci. 40, 407–418 (2015)

    Article  PubMed  CAS  Google Scholar 

  8. Ledeen, R.W., Wu, G., Lu, Z.H., Kozireski-Chuback, D., Fang, Y.: The role of GM1 and other gangliosides in neuronal differentiation overview and new finding. Ann. N.Y. Acad. Sci. 845, 161–175 (1998)

    Article  PubMed  CAS  Google Scholar 

  9. Ledeen, R., Wu, G.: Gangliosides of the Nervous System. Methods Mol. Biol. 1804, 19–55 (2018)

    Article  PubMed  CAS  Google Scholar 

  10. Guo, Z.: Ganglioside GM1 and the Central Nervous System. Int. J. Mol. Sci. 24, (2023)

  11. Chiricozzi, E., Lunghi, G., Di Biase, E., Fazzari, M., Sonnino, S., Mauri, L.: GM1 Ganglioside is a key factor in maintaining the mammalian neuronal functions avoiding neurodegeneration. Int. J. Mol. Sci. 21, (2020)

  12. Brocca, P., Berthault, P., Sonnino, S.: Conformation of the oligosaccharide chain of G(M1) ganglioside in a carbohydrate-enriched surface. Biophys. J. 74, 309–318 (1998)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Brocca, P., Bernardi, A., Raimondi, L., Sonnino, S.: Modeling ganglioside headgroups by conformational analysis and molecular dynamics. Glycoconj. J. 17, 283–299 (2000)

    Article  PubMed  CAS  Google Scholar 

  14. Yagi-Utsumi, M., Kameda, T., Yamaguchi, Y., Kato, K.: NMR characterization of the interactions between lyso-GM1 aqueous micelles and amyloid beta. FEBS Lett. 584, 831–836 (2010)

    Article  PubMed  CAS  Google Scholar 

  15. Yagi-Utsumi, M., Kato, K.: Structural and dynamic views of GM1 ganglioside. Glycoconj. J. 32, 105–112 (2015)

    Article  PubMed  CAS  Google Scholar 

  16. Acquotti, D., Poppe, L., Dabrowski, J., Von der Lieth, C.W., Sonnino, S., Tettamanti, G.: Three-dimensional structure of the oligosaccharide chain of GM1 ganglioside revealed by a distance-mapping procedure: a rotating and laboratory frame nuclear overhauser enhancement investigation of native glycolipid in dimethyl sulfoxide and in water-dodecylphosphocholine solutions. J. Am. Chem. Soc. 7772–7778 (1990)

  17. Chiricozzi, E., Di Biase, E., Lunghi, G., Fazzari, M., Loberto, N., Aureli, M., Mauri, L., Sonnino, S.: Turning the spotlight on the oligosaccharide chain of GM1 ganglioside. Glycoconj. J. 38, 101–117 (2021)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Chiricozzi, E., Pomè, D.Y., Maggioni, M., Di Biase, E., Parravicini, C., Palazzolo, L., Loberto, N., Eberini, I., Sonnino, S.: Role of the GM1 ganglioside oligosaccharide portion in the TrkA-dependent neurite sprouting in neuroblastoma cells. J. Neurochem. 143, 645–659 (2017)

    Article  PubMed  CAS  Google Scholar 

  19. Chiricozzi, E., Maggioni, M., di Biase, E., Lunghi, G., Fazzari, M., Loberto, N., Elisa, M., Scalvini, F.G., Tedeschi, G., Sonnino, S.: The Neuroprotective Role of the GM1 Oligosaccharide, II3Neu5Ac-Gg4, in neuroblastoma cells. Mol. Neurobiol. 56, 6673–6702 (2019)

    Article  PubMed  CAS  Google Scholar 

  20. Fazzari, M., Di Biase, E., Zaccagnini, L., Henriques, A., Callizot, N., Ciampa, M.G., Mauri, L., Carsana, E.V., Loberto, N., Aureli, M., Mari, L., Civera, M., Vasile, F., Sonnino, S., Bartels, T., Chiricozzi, E., Lunghi, G.: GM1 oligosaccharide efficacy against α-synuclein aggregation and toxicity in vitro. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1868, 159350 (2023)

  21. Wiegandt, H., Bücking, H.W.: Carbohydrate components of extraneuronal gangliosides from bovine and human spleen, and bovine kidney. Eur. J. Biochem. 15, 287–292 (1970)

    Article  PubMed  CAS  Google Scholar 

  22. Tettamanti, G., Bonali, F., Marchesini, S., Zambotti, V.: A new procedure for the extraction, purification and fractionation of brain gangliosides. Biochim. Biophys. Acta 296, 160–170 (1973)

    Article  PubMed  CAS  Google Scholar 

  23. Acquotti, D., Cantù, L., Ragg, E., Sonnino, S.: Geometrical and conformational properties of ganglioside GalNAc-GD1a, IV4GalNAcIV3Neu5AcII3Neu5AcGgOse4Cer. Eur. J. Biochem. 225, 271–288 (1994)

    Article  PubMed  CAS  Google Scholar 

  24. Imamura, A., Yoshikawa, T., Komori, T., Ando, M., Ando, H., Wakao, M., Suda, Y., Ishida, H., Kiso, M.: Design and synthesis of versatile ganglioside probes for carbohydrate microarrays. Glycoconj. J. 25, 269–278 (2008)

    Article  PubMed  CAS  Google Scholar 

  25. Chiricozzi, E., Biase, E.D., Maggioni, M., Lunghi, G., Fazzari, M., Pomè, D.Y., Casellato, R., Loberto, N., Mauri, L., Sonnino, S.: GM1 promotes TrkA-mediated neuroblastoma cell differentiation by occupying a plasma membrane domain different from TrkA. J. Neurochem. 149, 231–241 (2019)

    Article  PubMed  CAS  Google Scholar 

  26. Sonnino, S., Cantù, L., Corti, M., Acquotti, D., Venerando, B.: Aggregative properties of gangliosides in solution. Chem. Phys. Lipids 71, 21–45 (1994)

    Article  PubMed  CAS  Google Scholar 

  27. Corti, M., Degiorgio, V., Ghidoni, R., Sonnino, S., Tettamanti, G.: Laser-light scattering investigation of the micellar properties of gangliosides. Chem. Phys. Lipids 26, 225–238 (1980)

    Article  PubMed  CAS  Google Scholar 

  28. Ulrich-Bott, B., Wiegandt, H.: Micellar properties of glycosphingolipids in aqueous media. J. Lipid Res. 25, 1233–1245 (1984)

    Article  PubMed  CAS  Google Scholar 

  29. Valsecchi, M., Chigorno, V., Sonnino, S., Tettamanti, G.: Rat cerebellar granule cells in culture associate and metabolize differently exogenous GM1 ganglioside molecular species containing a C18 or C20 long chain base. Chem. Phys. Lipids 60, 247–252 (1992)

    Article  PubMed  CAS  Google Scholar 

  30. Di Biase, E., Lunghi, G., Fazzari, M., Maggioni, M., Pomè, D.Y., Valsecchi, M., Samarani, M., Fato, P., Ciampa, M.G., Prioni, S., Mauri, L., Sonnino, S., Chiricozzi, E.: Gangliosides in the differentiation process of primary neurons: the specific role of GM1-oligosaccharide. Glycoconj. J. 37, 329–343 (2020)

    Article  PubMed  Google Scholar 

  31. Schengrund, C.L., Prouty, C.: Oligosaccharide portion of GM1 enhances process formation by S20Y neuroblastoma cells. J. Neurochem. 51, 277–282 (1988)

    Article  PubMed  CAS  Google Scholar 

  32. Schneider, C.A., Rasband, W.S., Eliceiri, K.W.: NIH Image to ImageJ: 25 years of image analysis. Nat. Methods 9, 671–675 (2012)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Aureli, M., Bassi, R., Prinetti, A., Chiricozzi, E., Pappalardi, B., Chigorno, V., Di Muzio, N., Loberto, N., Sonnino, S.: Ionizing radiations increase the activity of the cell surface glycohydrolases and the plasma membrane ceramide content. Glycoconj. J. 29, 585–597 (2012)

    Article  PubMed  CAS  Google Scholar 

  34. Wehrman, T., He, X., Raab, B., Dukipatti, A., Blau, H., Garcia, K.C.: Structural and mechanistic insights into nerve growth factor interactions with the TrkA and p75 receptors. Neuron 53, 25–38 (2007)

    Article  PubMed  CAS  Google Scholar 

  35. Park, S.J., Lee, J., Qi, Y., Kern, N.R., Lee, H.S., Jo, S., Joung, I., Joo, K., Im, W.: CHARMM-GUI Glycan Modeler for modeling and simulation of carbohydrates and glycoconjugates. Glycobiology 29, 320–331 (2019)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Naïm, M., Bhat, S., Rankin, K.N., Dennis, S., Chowdhury, S.F., Siddiqi, I., Drabik, P., Sulea, T., Bayly, C.I., Jakalian, A., Purisima, E.O.: Solvated interaction energy (SIE) for scoring protein-ligand binding affinities. 1. Exploring the parameter space. J. Chem. Inf. Model. 47, 122–133 (2007)

    Article  PubMed  Google Scholar 

  37. Biller, J.R., Elajaili, H., Meyer, V., Rosen, G.M., Eaton, S.S., Eaton, G.R.: Electron spin-lattice relaxation mechanisms of rapidly-tumbling nitroxide radicals. J. Magn. Reson. 236, 47–56 (2013)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Facci, L., Leon, A., Toffano, G., Sonnino, S., Ghidoni, R., Tettamanti, G.: Promotion of neuritogenesis in mouse neuroblastoma cells by exogenous gangliosides. Relationship between the effect and the cell association of ganglioside GM1. J. Neurochem. 42, 299–305 (1984)

    Article  PubMed  CAS  Google Scholar 

  39. Farooqui, T., Franklin, T., Pearl, D.K., Yates, A.J.: Ganglioside GM1 enhances induction by nerve growth factor of a putative dimer of TrkA. J. Neurochem. 68, 2348–2355 (1997)

    Article  PubMed  CAS  Google Scholar 

  40. Singleton, D.W., Lu, C.L., Colella, R., Roisen, F.J.: Promotion of neurite outgrowth by protein kinase inhibitors and ganglioside GM1 in neuroblastoma cells involves MAP kinase ERK1/2. Int. J. Dev. Neurosci. 18, 797–805 (2000)

    Article  PubMed  CAS  Google Scholar 

  41. Rabin, S.J., Bachis, A., Mocchetti, I.: Gangliosides activate Trk receptors by inducing the release of neurotrophins. J. Biol. Chem. 277, 49466–49472 (2002)

    Article  PubMed  CAS  Google Scholar 

  42. Duchemin, A.M., Ren, Q., Mo, L., Neff, N.H., Hadjiconstantinou, M.: GM1 ganglioside induces phosphorylation and activation of Trk and Erk in brain. J. Neurochem. 81, 696–707 (2002)

    Article  PubMed  CAS  Google Scholar 

  43. Da Silva, J.S., Hasegawa, T., Miyagi, T., Dotti, C.G., Abad-Rodriguez, J.: Asymmetric membrane ganglioside sialidase activity specifies axonal fate. Nat. Neurosci. 8, 606–615 (2005)

    Article  PubMed  Google Scholar 

  44. Mocchetti, I.: Exogenous gangliosides, neuronal plasticity and repair, and the neurotrophins. Cell. Mol. Life Sci. 62, 2283–2294 (2005)

    Article  PubMed  CAS  Google Scholar 

  45. Zakharova, I.O., Sokolova, T.V., Vlasova, Y.A., Furaev, V.V., Rychkova, M.P., Avrova, N.F.: GM1 ganglioside activates ERK1/2 and Akt downstream of Trk tyrosine kinase and protects PC12 cells against hydrogen peroxide toxicity. Neurochem. Res. 39, 2262–2275 (2014)

    Article  PubMed  CAS  Google Scholar 

  46. Huang, E.J., Reichardt, L.F.: Trk receptors: roles in neuronal signal transduction. Annu. Rev. Biochem. 72, 609–642 (2003)

    Article  PubMed  CAS  Google Scholar 

  47. Byrne, M.C., Ledeen, R.W., Roisen, F.J., Yorke, G., Sclafani, J.R.: Ganglioside-induced neuritogenesis: verification that gangliosides are the active agents, and comparison of molecular species. J. Neurochem. 41, 1214–1222 (1983)

    Article  PubMed  CAS  Google Scholar 

  48. Nagai, Y.: Functional roles of gangliosides in bio-signaling. Behav. Brain Res. 66, 99–104 (1995)

    Article  PubMed  CAS  Google Scholar 

  49. Skaper, S.D., Katoh-Semba, R., Varon, S.: GM1 ganglioside accelerates neurite outgrowth from primary peripheral and central neurons under selected culture conditions. Brain Res. 355, 19–26 (1985)

    Article  PubMed  CAS  Google Scholar 

  50. Valaperta, R., Valsecchi, M., Rocchetta, F., Aureli, M., Prioni, S., Prinetti, A., Chigorno, V., Sonnino, S.: Induction of axonal differentiation by silencing plasma membrane-associated sialidase Neu3 in neuroblastoma cells. J. Neurochem. 100, 708–719 (2007)

    Article  PubMed  CAS  Google Scholar 

  51. Pshezhetsky, A.V., Ashmarina, M.: Keeping it trim: roles of neuraminidases in CNS function. Glycoconj. J. 35, 375–386 (2018)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Ledeen, R.W., Wu, G., Cannella, M.S., Oderfeld-Nowak, B., Cuello, A.C.: Gangliosides as neurotrophic agents: studies on the mechanism of action. Acta Neurobiol. Exp. (Wars) 50, 439–449 (1990)

    PubMed  CAS  Google Scholar 

  53. Ferrari, G., Anderson, B.L., Stephens, R.M., Kaplan, D.R., Greene, L.A.: Prevention of apoptotic neuronal death by GM1 ganglioside: Involvement of Trk neurotrophin receptors. J. Biol. Chem. 270, 3074–3080 (1995)

    Article  PubMed  CAS  Google Scholar 

  54. Mutoh, T., Tokuda, A., Miyadai, T., Hamaguchi, M., Fujiki, N.: Ganglioside GM1 binds to the Trk protein and regulates receptor function. Proc. Natl. Acad. Sci. U.S.A. 92, 5087–5091 (1995)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Mutoh, T., Tokuda, A., Inokuchi, J., Kuriyama, M.: Glucosylceramide synthase inhibitor inhibits the action of nerve growth factor in PC12 cells. J. Biol. Chem. 273, 26001–26007 (1998)

    Article  PubMed  CAS  Google Scholar 

  56. Bachis, A., Rabin, S.J., Del Fiacco, M., Mocchetti, I.: Gangliosides prevent excitotoxicity through activation of TrkB receptor. Neurotox. Res. 4, 225–234 (2002)

    Article  PubMed  CAS  Google Scholar 

  57. Kappagantula, S., Andrews, M.R., Cheah, M., Abad-Rodriguez, J., Dotti, C.G., Fawcett, J.W.: Neu3 sialidase-mediated ganglioside conversion is necessary for axon regeneration and is blocked in CNS axons. J. Neurosci. 34, 2477–2492 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Manev, H., Favaron, M., Vicini, S., Guidotti, A., Costa, E.: Glutamate-induced neuronal death in primary cultures of cerebellar granule cells: protection by synthetic derivatives of endogenous sphingolipids. J. Pharmacol. Exp. Ther. 252, 419–427 (1990)

    PubMed  CAS  Google Scholar 

  59. Costa, E., Armstrong, D., Guidotti, A., Kharlamov, A., Kiedrowski, L., Wroblewski, J.T.: Ganglioside GM1 and its semisynthetic lysogangliosides reduce glutamate neurotoxicity by a novel mechanism. Adv. Exp. Med. Biol. 341, 129–141 (1993)

    Article  PubMed  CAS  Google Scholar 

  60. Kharlamov, A., Guidotti, A., Costa, E., Hayes, R., Armstrong, D.: Semisynthetic sphingolipids prevent protein kinase C translocation and neuronal damage in the perifocal area following a photochemically induced thrombotic brain cortical lesion. J. Neurosci. 13, 2483–2494 (1993)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Saito, M., Berg, M.J., Guidotti, A., Marks, N.: Gangliosides attenuate ethanol-induced apoptosis in rat cerebellar granule neurons. Neurochem. Res. 24, 1107–1115 (1999)

    Article  PubMed  CAS  Google Scholar 

  62. Hadaczek, P., Wu, G., Sharma, N., Ciesielska, A., Bankiewicz, K., Davidow, A.L., Lu, Z.H., Forsayeth, J., Ledeen, R.W.: GDNF signaling implemented by GM1 ganglioside; failure in Parkinson’s disease and GM1-deficient murine model. Exp. Neurol. 263, 177–189 (2015)

  63. Aureli, M., Mauri, L., Carsana, E.V., Dobi, D., Breviario, S., Lunghi, G., Sonnino, S.: Gangliosides and Cell Surface Ganglioside Metabolic Enzymes in the Nervous System. Adv. Neurobiol. 29, 305–332 (2023)

    Article  PubMed  Google Scholar 

  64. Cirillo, F., Ghiroldi, A., Fania, C., Piccoli, M., Torretta, E., Tettamanti, G., Gelfi, C., Anastasia, L.: NEU3 Sialidase Protein Interactors in the Plasma Membrane and in the Endosomes. J. Biol. Chem. 291, 10615–10624 (2016)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Venerando, B., Cestaro, B., Fiorilli, A., Ghidoni, R., Preti, A., Tettamanti, G.: Kinetics of Vibrio cholerae sialidase action on gangliosidic substrates at different supramolecular-organizational levels. Biochem. J. 203, 735–742 (1982)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Monti, E., Bassi, M.T., Papini, N., Riboni, M., Manzoni, M., Venerando, B., Croci, G., Preti, A., Ballabio, A., Tettamanti, G., Borsani, G.: Identification and expression of NEU3, a novel human sialidase associated to the plasma membrane. Biochem. J. 349, 343–351 (2000)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Hata, K., Wada, T., Hasegawa, A., Kiso, M., Miyagi, T.: Purification and characterization of a membrane-associated ganglioside sialidase from bovine brain. J. Biochem. 123, 899–905 (1998)

    Article  PubMed  CAS  Google Scholar 

  68. Hasegawa, T., Yamaguchi, K., Wada, T., Takeda, A., Itoyama, Y., Miyagi, T.: Molecular cloning of mouse ganglioside sialidase and its increased expression in Neuro2a cell differentiation. J. Biol. Chem. 275, 8007–8015 (2000)

    Article  PubMed  CAS  Google Scholar 

  69. Preti, A., Fiorilli, A., Lombardo, A., Caimi, L., Tettamanti, G.: Occurrence of sialyltransferase activity in the synaptosomal membranes prepared from calf brain cortex. J. Neurochem. 35, 281–296 (1980)

    Article  PubMed  CAS  Google Scholar 

  70. Crespo, P.M., Demichelis, V.T., Daniotti, J.L.: Neobiosynthesis of glycosphingolipids by plasma membrane-associated glycosyltransferases. J. Biol. Chem. 285, 29179–29190 (2010)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Ottico, E., Prinetti, A., Prioni, S., Giannotta, C., Basso, L., Chigorno, V., Sonnino, S.: Dynamics of membrane lipid domains in neuronal cells differentiated in culture. J. Lipid Res. 44, 2142–2151 (2003)

    Article  PubMed  CAS  Google Scholar 

  72. Varki, A., Cummings, R.D., Aebi, M., Packer, N.H., Seeberger, P.H., Esko, J.D., Stanley, P., Hart, G., Darvill, A., Kinoshita, T., Prestegard, J.J., Schnaar, R.L., Freeze, H.H., Marth, J.D., Bertozzi, C.R., Etzler, M.E., Frank, M., Vliegenthart, J.F., Lütteke, T., Perez, S., Bolton, E., Rudd, P., Paulson, J., Kanehisa, M., Toukach, P., Aoki-Kinoshita, K.F., Dell, A., Narimatsu, H., York, W., Taniguchi, N., Kornfeld, S.: Symbol Nomenclature for Graphical Representations of Glycans. Glycobiology 25, 1323–1324 (2015)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Funding

E.C. was supported by PSR 2019, University of Milano. L.M. was supported by RV_TAR16SSONN_M. I.E., L.P., Si.Sa. and O.B.M. were supported by MIUR “Progetto d’Eccellenza 2023–2025”. L.P. was supported by PSR 2022, University of Milano.

Author information

Author notes

  1. Maria Fazzari and Giulia Lunghi are equally contributed to this work.

Authors and Affiliations

  1. Department of Medical Biotechnology and Translational Medicine, University of Milano, Segrate, Milano, Italy

    Maria Fazzari, Giulia Lunghi, Erika Di Biase, Margherita Maggioni, Emma Veronica Carsana, Laura Cioccarelli, Laura Vigani, Nicoletta Loberto, Massimo Aureli, Laura Mauri, Maria Grazia Ciampa, Manuela Valsecchi, Elena Chiricozzi & Sandro Sonnino

  2. Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan

    Koichi Takato

  3. Department of Applied Bioorganic Chemistry, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan

    Akihiro Imamura & Hideharu Ishida

  4. Institute for Glyco-core Research (iGCORE), Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan

    Akihiro Imamura & Hideharu Ishida

  5. Dipartimento di Scienze Farmacologiche e Biomolecolari “Rodolfo Paoletti”, Università degli Studi di Milano, Milano, Italy

    Omar Ben Mariem, Luca Palazzolo & Ivano Eberini

  6. Analytical Excellence & Program Management, Merck Serono S.p.A, Rome, Italy

    Simona Saporiti

  7. Data Science Research Center, Università degli Studi di Milano, Milano, Italy

    Ivano Eberini

Authors
  1. Maria Fazzari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giulia Lunghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Erika Di Biase
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Margherita Maggioni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Emma Veronica Carsana
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Laura Cioccarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Laura Vigani
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nicoletta Loberto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Massimo Aureli
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Laura Mauri
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Maria Grazia Ciampa
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Manuela Valsecchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Koichi Takato
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Akihiro Imamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Hideharu Ishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Omar Ben Mariem
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Simona Saporiti
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Luca Palazzolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Elena Chiricozzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Ivano Eberini
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Sandro Sonnino
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, methodology, investigation, analysis, and draft of the manuscript, M.F., G.L., E.D.B.; M.M., E.V.C., L.C., L.V., E.C., Si.Sa., O.B.M., L.P., I.E., M.A., N.L., M.G.C. Supervision, conceptualization, draft and revision of the manuscript, M.F., G.L., Sa.So., I.E., E.C.; GM1 and derivatives chemical synthesis, L.M., M.G.C., K.T., A.I., H.I., Docking Analysis: I.E., O.B.M., Si.Sa., L.P.; All authors have revised, read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Elena Chiricozzi or Sandro Sonnino.

Ethics declarations

Conflicts of interests

The authors declare that they have no conflicts of interests.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed Consent Statement

Not applicable.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 1627 KB)

Supplementary file2 (PDF 628 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fazzari, M., Lunghi, G., Di Biase, E. et al. GM1 structural requirements to mediate neuronal functions. Glycoconj J 40, 655–668 (2023). https://doi.org/10.1007/s10719-023-10141-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-023-10141-8

Keywords

Search

Navigation