Post-translational Regulation of l-Glutamic Acid Decarboxylase in the Brain

Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. GABA is converted from glutamic acid by the action of glutamic acid decarboxylase (GAD). There are two forms of GAD in the brain, GAD65 and GAD67, referring to a molecular weight of 65 and 67 kDa, respectively. Perturbations in GABAergic neurotransmission have been linked to a number of neurological disorders. Since GAD is the rate-limiting enzyme in controlling GABA synthesis, it is important to understand how GAD is regulated in the brain. It is known that GAD function can be regulated at the transcriptional/translational and post-translational levels. This review focuses briefly on the recent advances in revealing the post-translational regulation of GAD function including protein phosphorylation, palmitoylation and activity-dependent cleavage. The results from these studies have improved our understanding of the regulation of GAD function in the brain.