GM1 neurotrophic properties are related to GM1 oligosaccharide - TRKA interaction.

Several data suggest a specific role of ganglioside GM1 in neuronal differentiation and development, but the molecular mechanisms of these processes are largely unknown. The involvement of GM1 ganglioside in the process of neurite production has been reported for many years. Here, we report that the only GM1 oligosaccharide, rather than the ceramide portion or the total molecule, is directly involved in these processes. GM1, or its oligosaccharide, was added to the neuroblastoma cell culture medium and neurite outgrowth evaluation was accomplished by phase contrast microscopy; neurofilament expression and Trk pathway activation were evaluate by Western Blotting. GM1 oligosaccharide induced neuritogenesis and stimulated Trk pathway activation. Neurite elongation was accompanied by an increase of the neurofilament protein expression. The comparison of the results obtained with GM1 suggests a direct action of GM1 oligosaccharide in the neuritogenesis processes and in Trk activation in murine neuroblastoma cells. This means that the specific role exerted by changes of the membrane ganglioside GM1 content, described in the past, is determined by a direct interaction between the GM1 oligosaccharide portion and specific proteins. This allows considering both the trans- and cis -interaction via a head-to-head and side-by-side interaction, respectively. Trk receptor is involved in the process by direct interaction or by interaction through intermediate proteins.