GM1 neurotrophic properties are related to gm1oligosaccharide - TrkA interaction in mouse neuroblastoma cells

Experimental evidence, both in vitro and in vivo, highlight the neurotrophic and neurodifferentiative effects of ganglioside GM1. So far, the molecular mechanism underlining the GM1 neuro activities is still unknown. In order to clarify the molecular mechanism by which GM1 exerts its neurotrophic action we decide to investigate the importance of its oligosaccharide portion. Here, we describe the specific role of the GM1 oligosaccharide in promoting differentiation in neuron like cells. GM1 oligosaccharide was added to the culture medium of murine neuroblastoma N2a cells. To study the neurodifferentiation, cells were followed over the time to assess both morphological parameters and biochemical markers. In murine neuroblastoma cell lines we found that the oligosaccharide chain of GM1 is directly involved in the processes of neuronal differentiation by inducing TrkA-MAPK pathway activation. By biochemical and structural analysis we demonstrated a direct interaction at the plasma membrane level between the GM1 oligosaccharidic chain and TrkA receptor. We surmise that the neurotrophic effect of GM1 is due to a direct interaction between the oligosaccharide chain and TrkA receptor. This evidence leads us to consider both the trans- and cis interaction via head-to-head and side-by-side interaction, respectively.