The δ2 glutamate receptor:: a key molecule controlling synaptic plasticity and structure in Purkinje cells
The δ2 glutamate receptor:: a key molecule controlling synaptic plasticity and structure in Purkinje cells
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DOI：
10.1080/14734220410028921
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发表时间：
2004-01-01
期刊：
影响因子：
3.5
通讯作者：
Yuzaki, M
中科院分区：
文献类型：
--
作者：
Yuzaki, M
孤儿谷氨酸受体δ 2（GluRdelta 2）主要在小脑浦肯野细胞中表达，在小脑功能中起着至关重要的作用;缺乏GluRdelta 2基因的小鼠表现出共济失调和运动相关学习任务受损。然而，当单独表达或与其他谷氨酸受体一起表达时，GluRdelta 2不形成功能性谷氨酸门控离子通道，也不与谷氨酸类似物结合。因此，GluRdelta 2参与小脑功能的机制一直难以捉摸。对突变小鼠（如lurcher、hotfoot和GluRdelta 2敲除小鼠）的研究为GluRdelta 2的结构和功能提供了线索。特别是，hotfoot和GluRdelta 2基因敲除小鼠的形态学和电生理学分析表明，GluRdelta 2在平行纤维（PF）-浦肯野细胞突触的突触后元件与突触前元件对齐和维持中具有独特的作用。此外，GluRdelta 2在成年小脑电活动阻断后新形成的异位PF-浦肯野细胞突触中表达。此外，GluRdelta 2的细胞外N-末端区域的特异性抗体的应用废除了突触可塑性。这些结果表明，GluRdelta 2在成年小鼠突触形成和突触可塑性中起直接作用。基于这些结果，本文提出了GluRdelta 2功能机制的两个假说。
The orphan glutamate receptor delta2 (GluRdelta2) is predominantly expressed in cerebellar Purkinje cells and plays a crucial role in cerebellar functions; mice that lack the GluRdelta2 gene display ataxia and impaired motor-related learning tasks. However, when expressed alone or with other glutamate receptors, GluRdelta2 does not form functional glutamate-gated ion channels nor does it bind to glutamate analogs. Therefore, the mechanisms by which GluRdelta2 participates in cerebellar functions have been elusive. Studies of mutant mice, such as lurcher, hotfoot, and GluRdelta2 knockout mice, have provided clues to the structure and function of GluRdelta2. Particularly, morphological and electrophysiological analyses of hotfoot and GluRdelta2 knockout mice have indicated a unique role of GluRdelta2 in aligning and maintaining the postsynaptic element with the presynaptic one at parallel fiber (PF)-Purkinje cell synapses. In addition, GluRdelta2 was expressed in newly formed ectopic PF-Purkinje cell synapses found after blockade of electrical activity in adult cerebellum. Moreover, application of an antibody specific for GluRdelta2's extracellular N-terminal region abrogated synaptic plasticity. These results indicate that GluRdelta2 plays a direct role in synapse formation and synaptic plasticity in adult mice. Based on these results, two hypotheses about mechanisms by which GluRdelta2 functions are proposed in this article.