Requirement of GM2 ganglioside activator for phospholipase D activation

Sequence analysis of a heat-stable protein necessary for the activation of ADP ribosylation factor-dependent phospholipase D (PLD) reveals that this protein has a structure highly homologous to the previously known G(M2) ganglioside activator whose deficiency results in the AB-variant of G(M2) gangliosidosis. The heat-stable activator protein indeed has the capacity to enhance enzymatic conversion of G(M2) to G(M3) ganglioside that is catalyzed by beta-hexosaminidase A. Inversely, G(M2) ganglioside activator purified separately from tissues as described earlier [Conzelmann, E. & Sandhoff, K. (1987) Methods Enzymol, 138, 792-815] stimulates ADP ribosylation factor dependent PLD in a dose-dependent manner. At higher concentrations of ammonium sulfate, the PLD activator protein apparently substitutes for protein kinase C and phosphatidylinositol 4,5-bisphosphate, both of which are known as effective stimulators of the PLD reaction. The mechanism of action of the heat-stable PLD activator protein remains unknown.