Sugiura N, Patel R G, Corriveau R A
Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan 48201, USA.
J Biol Chem. 2001 Apr 27;276(17):14257-63. doi: 10.1074/jbc.M100011200. Epub 2001 Jan 31.
Mammalian brain development requires the transmission of electrical signals between neurons via the N-methyl-d-aspartate (NMDA) class of glutamate receptors. However, little is known about how NMDA receptors carry out this role. Here we report the first genes shown to be regulated by physiological levels of NMDA receptor function in developing neurons in vivo: NMDA receptor-regulated gene 1 (NARG1), NARG2, and NARG3. These genes share several striking regulatory features. All three are expressed at high levels in the neonatal brain in regions of neuronal proliferation and migration, are dramatically down-regulated during early postnatal development, and are down-regulated by NMDA receptor function. NARG2 and NARG3 appear to be novel, while NARG1 is the mammalian homologue of a yeast N-terminal acetyltransferase that regulates entry into the G(o) phase of the cell cycle. The results suggest that highly specific NMDA receptor-dependent regulation of gene expression plays an important role in the transition from proliferation of neuronal precursors to differentiation of neurons.
哺乳动物的大脑发育需要神经元之间通过N-甲基-D-天冬氨酸（NMDA）类谷氨酸受体传递电信号。然而，对于NMDA受体如何发挥这一作用，我们知之甚少。在此，我们报告了首批被证明在体内发育中的神经元中受NMDA受体功能生理水平调控的基因：NMDA受体调控基因1（NARG1）、NARG2和NARG3。这些基因具有几个显著的调控特征。这三个基因在新生大脑中神经元增殖和迁移区域均高水平表达，在出生后早期发育过程中显著下调，并受NMDA受体功能下调。NARG2和NARG3似乎是新发现的基因，而NARG1是酵母N-末端乙酰转移酶的哺乳动物同源物，该酶调节细胞周期进入G（o）期。结果表明，基因表达的高度特异性NMDA受体依赖性调控在神经元前体增殖向神经元分化的转变过程中发挥重要作用。
