谷氨酸 delta1 受体在前脑中的新兴图谱。
An emerging map of glutamate delta 1 receptors in the forebrain.
机构信息
Department of Pharmacology and Neuroscience, Creighton University, 2500 California Plaza, Omaha, NE, USA.
Department of Pharmacology and Neuroscience, Creighton University, 2500 California Plaza, Omaha, NE, USA.
出版信息
Neuropharmacology. 2021 Jul 1;192:108587. doi: 10.1016/j.neuropharm.2021.108587. Epub 2021 May 14.
Glutamate delta 1 (GluD1) and glutamate delta 2 (GluD2) form the delta family of ionotropic glutamate receptors; these proteins plays widespread roles in synaptic architecture, motor behavior, and cognitive function. Though the role of GluD2 at cerebellar parallel fiber-Purkinje cell synapses is well established, attention now turns to the function of GluD receptors in the forebrain. GluD1 regulates synaptic assembly and modulation in multiple higher brain regions, acting as a postsynaptic cell adhesion molecule with effects on both excitatory and inhibitory transmission. Furthermore, variations and mutations in the GRID1 gene, which codes for GluD1, and in genes which code for proteins functionally linked to GluD1, are associated with mental disorders including autism, schizophrenia, bipolar disorder, and major depression. Cerebellin (Cbln) family proteins, the primary binding partners of delta receptors, are secreted C1q-like proteins which also bind presynaptic neurexins (NRXNs), forming a tripartite synaptic bridge. Published research explores this bridge's function in regions including the striatum, hippocampus, cortex, and cerebellum. In this review, we summarize region- and circuit-specific functions and expression patterns for GluD1 and its related proteins, and their implications for behavior and disease.
谷氨酸 delta 1(GluD1)和谷氨酸 delta 2(GluD2)构成离子型谷氨酸受体的 delta 家族;这些蛋白在突触结构、运动行为和认知功能中发挥着广泛的作用。虽然 GluD2 在小脑平行纤维-浦肯野细胞突触中的作用已得到充分证实,但现在人们开始关注 GluD 受体在前脑中的功能。GluD1 调节多个高级脑区的突触组装和调制,作为一种突触后细胞粘附分子,对兴奋性和抑制性传递都有影响。此外,编码 GluD1 的 GRID1 基因和与 GluD1 功能相关的蛋白编码基因的变异和突变与包括自闭症、精神分裂症、双相情感障碍和重度抑郁症在内的精神障碍有关。Cbln 家族蛋白是 delta 受体的主要结合伴侣,是分泌的 C1q 样蛋白,也与突触前神经连接蛋白(NRXNs)结合,形成三部分突触桥。已发表的研究探讨了该桥在纹状体、海马体、皮层和小脑等区域的功能。在这篇综述中,我们总结了 GluD1 及其相关蛋白在特定区域和回路中的功能和表达模式,以及它们对行为和疾病的影响。