Modulation of Neurite Outgrowth and Ganglioside Associated Changes in Cerebral Neurons and PC12 Pheochromocytoma Cells

Abstract

The asymmetric position and molecular heterogeneity of gangliosides at the outer leaflet of the nerve plasma membrane has made this group of sialic acid containing glycosphingolipids a subject of expanding interest in neurobiology. Ever since the elucidation of the specific interaction between cholera toxin and GM1 (Moss and Vaughan, 1979; Bennet and Cuatrecasas, 1977) and the potential receptor function of gangliosides for thyrotropin hormone, a number of interactions between gangliosides and diverse ligands have been described (Kohn et al., 1981). Kohn and coworkers (1982) have suggested that gangliosides may serve as receptors for biologically active ligands to transduce signals across the bilayer. Basically, the model considers gangliosides as low affinity, high capacity binding sites which induce, upon interaction, conformational changes in the signal polypeptide. These changes evolve into additional short range hydrophobic interactions between the protein and the ganglioside which perturb the bilayer. An example for such perturbation is the generation of pores or channels in artificial bilayers which follows the interaction of cholera toxin (Tosteson and Tosteson, 1978) or tetanus toxin (Borochov-Neori et al., 1984) with the appropriate gangliosides.