A MEMBRANE FORM OF BRAIN L-GLUTAMATE DECARBOXYLASE - IDENTIFICATION, ISOLATION, AND ITS RELATION TO INSULIN-DEPENDENT DIABETES-MELLITUS

A membrane form of L-glutamate decarboxylase (GAD) was identified and purified to apparent homogeneity from hog brain. The purified GAD was established as an integral membrane protein by phase-partitioning assa y, charge-shift electrophoresis, and chromatography on a hydrophobic i nteraction column. This membrane GAD has a native molecular mass of 96 +/- 5 kDa and is a homodimer of 48 +/-3-kDa subunits. Immunoprecipita tion and immunoblotting tests revealed the presence of antibodies agai nst this membrane GAD in sera from patients with insulin-dependent dia betes mellitus. Since this form of GAD appears to be an integral membr ane protein and is presumed to have extracellular domains exposed, it seems reasonable to suggest that membrane GAD is more likely than solu ble GAD to be involved in the pathogenesis of insulin-dependent diabet es and related autoimmune disorders such as stiff-man syndrome.