Glutamic acid decarboxylase (GAD) is the enzyme responsible for synthesis of the 
neurotransmitter gamma-aminobutyric acid in neurons and pancreatic beta cells. 
It is represented by two isoforms, GAD-65 and GAD-67, which are the products of 
two different genes and differ substantially only at their N-terminal regions. 
GAD-65 is a dominant autoantigen in stiff-man syndrome and insulin-dependent 
diabetes mellitus. In neurons and beta cells, GAD is concentrated around 
synaptic vesicles and synaptic-like microvesicles, respectively, as well as in 
the area of the Golgi complex. The mechanisms responsible for specific targeting 
of GAD to these organelles are not yet understood. The elucidation of the 
mechanism of subcellular targeting of GAD may be relevant to understanding its 
role as an autoantigen. In this study, the cloned genes for GAD-65 and GAD-67 
were expressed separately in Chinese hamster ovary (CHO) cells and COS cells. 
While GAD-67 had a diffuse cytoplasmic localization, GAD-65 had a punctate 
distribution, with most of the immunoreactivity being concentrated in the area 
of the Golgi complex. A chimeric protein in which the 88 N-terminal amino acids 
of GAD-67 were replaced by the 83 N-terminal amino acids of GAD-65 was targeted 
to the Golgi complex, indicating that the N-terminal region of GAD-65 contains a 
targeting signal sufficient for directing the remaining portion of the molecule, 
highly similar in GAD-65 and GAD-67, to the Golgi complex-associated structures.