It has been recently reported by our group that GM1-oligosaccharide added to neuroblastoma cells or administered to mouse experimental model mimics the neurotrophic and neuroprotective properties of GM1 ganglioside. In addition to this, differently from GM1, GM1-oligosaccharide is not taken up by the cells, remaining solubilized into the extracellular environment interacting with cell surface proteins. Those characteristics make GM1-oligosaccharide a good tool to study the properties of the endogenous GM1, avoiding to interfere with the ganglioside natural metabolic pathway. In this study, we show that GM1-oligosaccharide administered to mice cerebellar granule neurons by interacting with cell surface induces TrkA-MAP kinase pathway activation enhancing neuron clustering, arborization and networking. Accordingly, in the presence of GM1-oligosaccharide, neurons show a higher phosphorylation rate of FAK and Src proteins, the intracellular key regulators of neuronal motility. Moreover, treated cells express increased level of specific neuronal markers, suggesting an advanced stage of maturation compared to controls. In parallel, we found that in the presence of GM1-oligosaccharide, neurons accelerate the expression of complex gangliosides and reduce the level of the simplest ones, displaying the typical ganglioside pattern of mature neurons. Our data confirms the specific role of GM1 in neuronal differentiation and maturation, determined by its oligosaccharide portion. GM1-oligosacchairide interaction with cell surface receptors triggers the activation of intracellular biochemical pathways responsible for neuronal migration, dendrites emission and axon growth.

Gangliosides in the differentiation process of primary neurons: the specific role of GM1-oligosaccharide / E. Di Biase, G. Lunghi, M. Fazzari, M. Maggioni, D.Y. Pomè, M. Valsecchi, M. Samarani, P. Fato, M.G. Ciampa, S. Prioni, L. Mauri, S. Sonnino, E. Chiricozzi. - In: GLYCOCONJUGATE JOURNAL. - ISSN 0282-0080. - 37:3(2020 Jun), pp. 329-343. [10.1007/s10719-020-09919-x]

Gangliosides in the differentiation process of primary neurons: the specific role of GM1-oligosaccharide

E. Di Biase
Primo
;
G. Lunghi;M. Fazzari;M. Maggioni;D.Y. Pomè;M. Valsecchi;M. Samarani;P. Fato;M.G. Ciampa;S. Prioni;L. Mauri;S. Sonnino;E. Chiricozzi
2020

Abstract

It has been recently reported by our group that GM1-oligosaccharide added to neuroblastoma cells or administered to mouse experimental model mimics the neurotrophic and neuroprotective properties of GM1 ganglioside. In addition to this, differently from GM1, GM1-oligosaccharide is not taken up by the cells, remaining solubilized into the extracellular environment interacting with cell surface proteins. Those characteristics make GM1-oligosaccharide a good tool to study the properties of the endogenous GM1, avoiding to interfere with the ganglioside natural metabolic pathway. In this study, we show that GM1-oligosaccharide administered to mice cerebellar granule neurons by interacting with cell surface induces TrkA-MAP kinase pathway activation enhancing neuron clustering, arborization and networking. Accordingly, in the presence of GM1-oligosaccharide, neurons show a higher phosphorylation rate of FAK and Src proteins, the intracellular key regulators of neuronal motility. Moreover, treated cells express increased level of specific neuronal markers, suggesting an advanced stage of maturation compared to controls. In parallel, we found that in the presence of GM1-oligosaccharide, neurons accelerate the expression of complex gangliosides and reduce the level of the simplest ones, displaying the typical ganglioside pattern of mature neurons. Our data confirms the specific role of GM1 in neuronal differentiation and maturation, determined by its oligosaccharide portion. GM1-oligosacchairide interaction with cell surface receptors triggers the activation of intracellular biochemical pathways responsible for neuronal migration, dendrites emission and axon growth.
GM1 ganglioside; GM1 oligosaccharide; Neurodifferentiation; Plasma membrane signaling; Primary neurons; TrkA neurotrophin receptor
Settore BIO/10 - Biochimica
   Dipartimenti di Eccellenza 2018-2022 - Dipartimento di FILOSOFIA
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
giu-2020
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/722767
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