PH-dependent Formation of Membranous Cytoplasmic Body-Like Structure of Ganglioside G M1/Bis(Monoacylglycero)Phosphate Mixed Membranes

Abstract

Membrane structures of the mixtures of ganglioside G M1 and endosome specific lipid, bis (monoacylglycero) phosphate (BMP, also known as lysobisphosphatidic acid) were examined at various pH conditions by freeze-fracture electron microscopy and small-angle x-ray scattering. At pH 8.5–6.5, a G M1/BMP (1:1 mol/mol) mixture formed small vesicular aggregates, whereas the mixture formed closely packed lamellar structures under acidic conditions (pH 5.5, 4.6) with the lamellar repeat distance of 8.06 nm. Since BMP alone exhibits a diffuse lamellar structure at a broad range of pH values and G M1 forms a micelle, the results indicate that both G M1 and BMP are required to produce closely stacked multilamellar vesicles. These vesicles resemble membranous cytoplasmic bodies in cells derived from patients suffering from G M1 gangliosidosis. Similar to G M1 gangliosidosis, cholesterol was trapped in BMP vesicles in G M1- and in a low pH-dependent manner. Studies employing different gangliosides and a G M1 analog suggest the importance of sugar chains and a sialic acid of G M1 in the pH-dependent structural change of G M1/BMP membranes.