Pinal C S, Tobin A J
Department of Biology, University of California, Los Angeles 90095, USA.
Perspect Dev Neurobiol. 1998;5(2-3):109-18.
GABA is present in organisms belonging to at least four of the five kingdoms. It acts as a neurotransmitter, a paracrine signaling molecule, a metabolic intermediate, or a trophic factor. In mammals, GABA synthesis depends on two forms of the enzyme glutamic acid decarboxylase--GAD65 and GAD67--that may serve distinctive functions within GABA-producing cells. The two GADs derive from two genes, which are differentially regulated, though nearly every GABA-producing cell contains both forms of GAD. GAD67 predominates early in development and after neuronal injury, consistent with a possible role in producing GABA for trophic use. In the embryo, GAD67 transcripts also undergo alternative splicing, which gives rise to truncated forms. In the mature neuron, GAD67 is present in both terminals and the cell body, where it may subserve a nonsynaptic, intracellular GABA pool. In contrast, GAD65 is usually expressed later in development and is primarily localized to nerve terminals. GAD65 enzymatic activity is more subject to regulation by cofactor binding and neuronal activity, consistent with its involvement in the production of synaptic GABA. Thus, while both GAD67 and GAD65 mediate the synthesis of GABA, their unique distributions and expression patterns suggest divergent functional roles.
γ-氨基丁酸（GABA）存在于至少五个生物界中四个界的生物体内。它可作为神经递质、旁分泌信号分子、代谢中间产物或营养因子。在哺乳动物中，GABA的合成依赖于两种形式的谷氨酸脱羧酶——GAD65和GAD67，它们可能在产生GABA的细胞内发挥独特功能。这两种GAD由两个基因衍生而来，它们受到不同的调控，不过几乎每个产生GABA的细胞都含有这两种形式的GAD。GAD67在发育早期和神经元损伤后占主导地位，这与它可能在产生用于营养作用的GABA方面发挥的作用一致。在胚胎中，GAD67转录本也会发生可变剪接，从而产生截短形式。在成熟神经元中，GAD67存在于终末和细胞体中，在那里它可能为非突触性细胞内GABA池提供支持。相比之下，GAD65通常在发育后期表达，并且主要定位于神经终末。GAD65的酶活性更易受到辅因子结合和神经元活动的调控，这与其参与突触GABA的产生一致。因此，虽然GAD67和GAD65都介导GABA的合成，但它们独特的分布和表达模式表明其功能作用存在差异。
