GANGLIOSIDE GM1 ALTERS NEURONAL MORPHOLOGY BY MODULATING THE ASSOCIATION OF MAP2 WITH MICROTUBULES AND ACTIN-FILAMENTS

In previous studies, we demonstrated that the exogenous ganglioside GM 1 increased the complexity of the microtubular network and level of tu bulin, selectively changed the distribution of microtubule associated protein-2 (MAP2) immunoreactivity from the perikarya to distal neuriti c processes and increased immunogold label of MAP2 in the subplasmalem mal cytoplasm, neuritic filopodia and growth cones of Neuro-2a neurobl astoma cells. Since these areas are rich in actin filaments, our data suggested that MAP2 may be associated with microfilaments in the early stages of ganglioside-induced neuritogenesis. To determine if GM1 alt ers neuronal morphology by facilitating the interaction of actin and M AP2, we examined the immunolocalization of these two proteins with con focal and electron microscopy. We found that along with the redistribu tion of MAP2 from perikaryal to neuritic regions, there was a parallel redistribution of actin. The uniform subplasmalemmal actin meshwork w as disrupted in areas of processes and filopodia with a redistribution of actin to these areas in close association with MAP2. Our present r esults suggest that gangliosides enhance neuritogenesis by redistribut ing actin as well as MAP2 to processes and filopodia thereby facilitat ing their interaction. The association of MAP2 with actin filaments is Likely to be an early step in ganglioside-mediated filopodia formatio n. (C) 1998 Elsevier Science B.V.