Behar T, Schaffner A, Laing P, Hudson L, Komoly S, Barker J
Laboratory of Neurophysiology, NINDS, NIH, Bethesda, MD 20898.
Brain Res Dev Brain Res. 1993 Apr 16;72(2):203-18. doi: 10.1016/0165-3806(93)90185-d.
At early developmental stages in the rat spinal cord (embryonic day 13), when neuronal progenitors are still proliferating, most differentiating neurons express truncated forms of glutamic acid decarboxylase (GAD) (approximately 25 kDa) which are the products of alternative splicing of the GAD67 gene. These truncated proteins do not appear to synthesize gamma-aminobutyric acid (GABA). The amino acid is detected in cells only after alternative splicing of the GAD67 gene generates a full-length, 67 kDa enzymatically active form of GAD. Both the 67 kDa GAD and GABA colocalize and appear diffusely distributed in the cytoplasm of embryonic neurons. GABA does not appear associated with synaptic vesicles until after birth, when its intracellular distribution becomes punctate and it colocalizes with synaptophysin. At this time, it also colocalizes with an immunologically distinct 65 kDa GAD protein encoded by a second GAD gene (GAD65). Expression of different GAD-related proteins with distinct intracellular distributions during development suggests that GABA, the product of these enzymes, may have trophic or metabolic roles during spinal cord differentiation.
在大鼠脊髓发育的早期阶段(胚胎第13天),当神经祖细胞仍在增殖时,大多数正在分化的神经元表达谷氨酸脱羧酶(GAD)的截短形式(约25 kDa),这些是GAD67基因可变剪接的产物。这些截短的蛋白质似乎不合成γ-氨基丁酸(GABA)。只有在GAD67基因的可变剪接产生全长的、67 kDa的具有酶活性的GAD形式后,才在细胞中检测到这种氨基酸。67 kDa的GAD和GABA共定位,并在胚胎神经元的细胞质中呈弥散分布。直到出生后,GABA才与突触小泡相关联,此时其细胞内分布变为点状,并与突触素共定位。此时,它还与由第二个GAD基因(GAD65)编码的免疫上不同的65 kDa GAD蛋白共定位。在发育过程中不同的与GAD相关的蛋白质具有不同的细胞内分布,这表明这些酶的产物GABA在脊髓分化过程中可能具有营养或代谢作用。