Evidence for a membrane surface defect in erythrocytes in Huntington's disease

Electron spin resonance studies of erythrocyte membranes from patients with Huntington's disease and normal controls have been performed. Intact erythrocytes in each case were either untreated or subjected to proteolysis with the membrane impermeable enzymes, pronase, chymotrypsin, or trypsin. Membrane ghosts were prepared from untreated and protease-treated intact cells and spin labeled with protein- or lipid-specific spin probes. Comparison of the resulting electron spin resonance spectra confirmed our previous findings that in untreated samples the relevant parameter of the protein-specific spin label was increased in Huntington's disease (P < 0.02) suggesting an altered physical state of membrane proteins in this disorder, while no difference in erythrocyte lipid fluidity could be discerned. No significant difference in the physical state of membrane proteins in Huntington's disease and control as judged as spin labeling methods could be detemined in membrane ghosts prepared from protease-treated intact cells. These results, together with the known specificity of the proteases used in this study, suggest that a molecular defect in Huntington's disease erythrocytes is manifested in an exterior part of a membrane protein and supports our hypothesis that Huntington's disease is associated with a generalized cell membrane defect.