SYNAPTIC VESICLE-ASSOCIATED GLUTAMATE-DECARBOXYLASE - IDENTIFICATION AND RELATIONSHIP TO INSULIN-DEPENDENT DIABETES-MELLITUS

Glutamic acid decarboxylase (GAD) catalyzes the biosynthesis of the in hibitory neurotransmitter gamma-aminobutyric acid (GABA), GAD has been suggested as an autoantigen in insulin-dependent diabetes mellitus an d stiff-man syndrome, Recently, three forms of membrane-associated GAD (MGAD) have been characterized in porcine brain, but the subcellular localization and function of these proteins are unknown, We present ev idence that GAD activity is associated with synaptic vesicles from por cine brain, These vesicles contain a 60 kDa protein recognized by seru m from patients with insulin-dependent diabetes mellitus, probably MGA DII, as shown by subcellular fractionation and immunoblotting, These r esults raise the possibility that the association of MGADII with synap tic vesicles may be crucial for its role as an autoantigen in insulin- dependent diabetes mellitus. (C) 1995 Wiley-Liss, Inc.