CLONING OF A NOVEL GLUTAMATE RECEPTOR SUBUNIT, GLUR5 - EXPRESSION IN THE NERVOUS-SYSTEM DURING DEVELOPMENT
CLONING OF A NOVEL GLUTAMATE RECEPTOR SUBUNIT, GLUR5 - EXPRESSION IN THE NERVOUS-SYSTEM DURING DEVELOPMENT
复制标题
DOI：
10.1016/0896-6273(90)90213-y
复制
发表时间：
1990-11-01
期刊：
影响因子：
16.2
通讯作者：
HEINEMANN, S
中科院分区：
文献类型：
--
作者：
BETTLER, B;BOULTER, J;HEINEMANN, S
我们已经分离到编码谷氨酸受体亚单位的cDNA，命名为CIuR5，与海氨酸/AMPA受体亚单位CIuR1、GIuR2、CIuR3和GIuR4的氨基酸同源性为40%-41%。这一序列相似性水平明显低于红藻氨酸/AMPA受体约70%的亚基间同源性特征。在非洲爪哇卵母细胞中，GIuR5蛋白形成同质离子通道，对L-谷氨酸反应微弱。GluR5基因在发育中的和成人的中枢和外周神经系统的神经元亚群中表达。在胚胎发育过程中，在神经元分化和突触形成的区域检测到GluR5转录本。前言：氨基酸L-谷氨酸是哺乳动物中枢神经系统中一种主要的兴奋性神经递质(Monaghan等，1989)。L-谷氨酸受体对突触的快速传递和突触的可塑性起重要作用(唐等，)和突触可塑性(Colingbridge和Bliss，1987)。突触可塑性很可能是通过改变突触效率来实现的，突触效率是由动作电位流经神经元回路触发的过程。相似或相同的机制有望在神经系统发育和记忆形成过程中产生灵活性。对这一观点的支持来自对谷氨酸受体的研究，特别是观察到谷氨酸受体参与了发育可塑性过程(Bear和Singer，1986；Kleinschmidt等人，1987；Woo等人，1987；Lipton和Kater，1989；Constantine-Paton等人，1990)，并在长时程增强中发挥作用，这是一种假设的记忆形成的电生理关联(Colingbridge and Bliss，1987；Kennedy，1989)。此外，谷氨酸受体的持续激活可能有助于癫痫、精神分裂症、亨廷顿病和阿尔茨海默病等疾病的发病(Olney，1989)。分子遗传学研究表明，神经递质受体的亚基是内源性的。
We have isolated cDNAs encoding a glutamate receptor subunit, designated CIuR5, displaying 40%-41% amino acid identity with the kainate/AMPA receptor subunits CIuRl, GIuR2, CIuR3, and GIuR4. This level of sequence similarity is significantly below the approximately 70% intersubunit identity characteristic of kainate/AMPA receptors. The GIuR5 protein forms homomeric ion channels in Xenopus oocytes that are weakly responsive to L-glutamate. The GluR5 gene is expressed in subsets of neurons throughout the developing and adult central and peripheral nervous systems. During embryogenesis, GluR5 transcripts are detected in areas of neuronal differentiation and synapse formation. introductionThe amino acid L-glutamate is a major excitatory neurotransmitter in the mammalian CNS (Monaghan et al., 1989). Receptors for L-glutamate are important for fast synaptic transmission (Tang et al., 1989) and synaptic plasticity (Collingridge and Bliss, 1987). Most likely, synaptic plasticity is achieved by modification of synaptic efficiency, a process triggered by the flow of action potentials through neuronal circuits. Similar or identical mechanisms are expected to generate flexibility in the nervous system both during development and in memory formation processes. Support for this idea derives from the study of glutamate receptors, specifically from the observations that they are involved in developmental plasticity processes (Bear and Singer, 1986; Kleinschmidt et al., 1987; Woo et al., 1987; Lipton and Kater, 1989; Constantine-Paton et al., 1990) and play a role in long-term potentiation, the postulated electrophysiological correlate of memory formation (Collingridge and Bliss, 1987; Kennedy, 1989). Furthermore, the continuous activation of glutamate receptors may contribute to the pathogenesis of diseases such as epilepsy, schizophrenia, Huntington’s disease, and Alzheimer’s disease (Olney, 1989). Molecular genetic studies have demonstrated that the subunits for neurotransmitter receptors are en-