Serine racemase: Activation by glutamate neurotransmission via glutamate receptor interacting protein and mediation of neuronal migration
Serine racemase: Activation by glutamate neurotransmission via glutamate receptor interacting protein and mediation of neuronal migration
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DOI：
10.1073/pnas.0409723102
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发表时间：
2005-02-08
影响因子：
11.1
通讯作者：
Snyder, SH
中科院分区：
文献类型：
--
作者：
Kim, PM;Aizawa, H;Snyder, SH
丝氨酸消旋酶（SR）定位于包裹突触的星形胶质细胞，将l -丝氨酸转化为d -丝氨酸，这是NMDA受体的内源性配体。我们报道了谷氨酸神经传递通过谷氨酸受体相互作用蛋白（GRIP）激活α -氨基-3-羟基-5-甲基异唑-4-丙酸受体，以及SR对小脑颗粒细胞迁移的生理调节。GRIP生理结合SR，增加SR活性和d -丝氨酸释放。新生小鼠小脑GRIP感染可增强颗粒细胞的体内迁移。d -丝氨酸被d -氨基酸氧化酶选择性降解和SR的药理学抑制阻碍了迁移，而d -丝氨酸则激活了这一过程。因此，在神经元迁移过程中，谷氨酸刺激伯格曼神经胶质形成并释放d -丝氨酸，d -丝氨酸与谷氨酸一起激活颗粒神经元上的NMDA受体，以趋化动力学的方式促进迁移。
Serine racemase (SR), localized to astrocytic glia that ensheathe synapses, converts L-serine to D-serine, an endogenous ligand of the NMDA receptor. We report the activation of SIR by glutamate neurotransmission involving alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors via glutamate receptor interacting protein (GRIP) and the physiologic regulation of cerebellar granule cell migration by SR. GRIP physiologically binds SR, augmenting SR activity and D-serine release. GRIP infection of neonatal mouse cerebellum in vivo enhances granule cell migration. Selective degradation Of D-serine by D-amino acid oxidase and pharmacologic inhibition of SR impede migration, whereas D-serine activates the process. Thus, in neuronal migration, glutamate stimulates Bergmann glia to form and release D-serine, which, together with glutamate, activates NMDA receptors on granule neurons, chemokinetically enhancing migration.