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Two Forms of the γ-Aminobutyric Acid Synthetic Enzyme Glutamate Decarboxylase Have Distinct Intraneuronal Distributions and Cofactor Interactions

Authors

  • Daniel L. Kaufman,

    1. Department of Biology, University of California at Los Angeles
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  • Carolyn R. Houser,

    1. Department of Anatomy and Cell Biology, University of California at Los Angeles
    2. Brain Research Institute, University of California at Los Angeles
    3. Veterans Administration Medical Center, West Los Angeles, Wadsworth Division, Los Angeles, California, U.S.A.
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  • Allan J. Tobin

    Corresponding author
    1. Department of Biology, University of California at Los Angeles
    2. Brain Research Institute, University of California at Los Angeles
    3. Molecular Biology Institute, University of California at Los Angeles
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  • The present address of Dr. D. L. Kaufman is Molecular Genetics Laboratory, The Salk Institute, P.O. Box 85800, San Diego, CA 92138, U.S.A.

Address correspondence and reprint requests to Dr. A. J. Tobin at Department of Biology, University of California at Los Angeles, Los Angeles, CA 90024-1606, U.S.A.

Abstract

Abstract: Glutamate decarboxylase (GAD) catalyzes the production of γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter. The mammalian brain contains two forms of GAD, with Ms of 67,000 and 65,000 (GAD67 and GAD65). Using a new antiserum specific for GAD67 and a monoclonal antibody specific for GAD65, we show that the two forms of GAD differ in their intraneuronal distributions: GAD67 is widely distributed throughout the neuron, whereas GAD65 lies primarily in axon terminals. In brain extracts, almost all GAD67 is in an active holoenzyme form, saturated with its cofactor, pyridoxal phosphate. In contrast, only about half of GAD65 (which is found in synaptic terminals) exists as active holoenzyme. We suggest that the relative levels of apo-GAD65 and holo-GAD65 in synaptic terminals may couple GABA production to neuronal activity.

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