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

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Abstract

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.

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Abbreviations

CSP:

Cysteine string protein

GAD:

Glutamic acid decarboxylase

HIP14:

Huntingtin interacting protein 14

HSP70:

Heat shock protein 70

IDDM:

Insulin-dependent diabetes mellitus

PAT:

Palmitoyl acyltransferase

PPT:

Protein palmitoyl thioesterase

SPS:

Stiff person syndrome

SV:

Synaptic vesicles

VGAT:

Vesicular GABA transporter

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Acknowledgment

This work was supported by the National Institutes of Health (NS37851 to J-Y Wu).

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Authors and Affiliations

  1. Department of Basic Science, Charles E. Schmidt College of Biomedical Science, Florida Atlantic University, Boca Raton, FL, 33431, USA

    Jianning Wei & Jang-Yen Wu

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  1. Jianning Wei
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  2. Jang-Yen Wu
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Correspondence to Jianning Wei or Jang-Yen Wu.

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Special issue article in honor of Dr. Ricardo Tapia.

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Wei, J., Wu, JY. Post-translational Regulation of l-Glutamic Acid Decarboxylase in the Brain. Neurochem Res 33, 1459–1465 (2008). https://doi.org/10.1007/s11064-008-9600-5

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  • DOI: https://doi.org/10.1007/s11064-008-9600-5

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