Luján R, Roberts J D, Shigemoto R, Ohishi H, Somogyi P
Department of Pharmacology, Oxford University, UK.
J Chem Neuroanat. 1997 Oct;13(4):219-41. doi: 10.1016/s0891-0618(97)00051-3.
Two group I metabotropic glutamate receptor subtypes, mGluR1 and mGluR5, have been reported to occur in highest concentration in an annulus surrounding the edge of the postsynaptic membrane specialisation. In order to determine whether such a distribution is uniform amongst postsynaptic mGluRs, their distribution was compared quantitatively by a pre-embedding silver-intensified immunogold technique at electron microscopic level in hippocampal pyramidal cells (mGluR5), cerebellar Purkinje cells (mGluR1 alpha) and Golgi cells (mGluR2). The results show that mGluR1 alpha, mGluR5 and mGluR2 each have a distinct distribution in relation to the glutamatergic synaptic junctions. On dendritic spines, mGluR1 alpha and mGluR5 showed the highest receptor density in a perisynaptic annulus (defined as within 60 nm of the edge of the synapse) followed by a decreasing extrasynaptic (60-900 nm) receptor level, but the gradient of decrease and the proportion of the perisynaptic pool (mGluR1 alpha, approximately 50%; vs mGluR5, approximately 25%) were different for the two receptors. The distributions of mGluR1 alpha and mGluR5 also differed significantly from simulated random distributions. In contrast, mGluR2 was not closely associated with glutamatergic synapses in the dendritic plasma membrane of cerebellar Golgi cells and its distribution relative to synapses is not different from simulated random distribution in the membrane. The somatic membrane, the axon and the synaptic boutons of the GABAergic Golgi cells also contained immunoreactive mGluR2 that is not associated with synaptic specialisations. In the hippocampal CA1 area the distribution of immunoparticles for mGluR5 on individual spines was established using serial sections. The results indicate that dendritic spines of pyramidal cells are heterogeneous with respect to the ratio of perisynaptic to extrasynaptic mGluR5 pools and about half of the immunopositive spines lack the perisynaptic pool. The quantitative comparison of receptor distributions demonstrates that mGluR1 alpha and mGluR5, but not mGluR2, are highly compartmentalised in different plasma membrane domains. The unique distribution of each mGluR subtype may reflect requirements for different transduction and effector mechanisms between cell types and different domains of the same cell, and suggests that the precise placement of receptors is a crucial factor contributing to neuronal communication.
据报道，两种I型代谢型谷氨酸受体亚型，即mGluR1和mGluR5，在突触后膜特化边缘周围的环状区域中浓度最高。为了确定这种分布在突触后mGluR中是否均匀，我们在电子显微镜水平上，采用包埋前银增强免疫金技术，对海马锥体细胞（mGluR5）、小脑浦肯野细胞（mGluR1α）和高尔基细胞（mGluR2）中它们的分布进行了定量比较。结果表明，mGluR1α、mGluR5和mGluR2在与谷氨酸能突触连接的关系上各有独特的分布。在树突棘上，mGluR1α和mGluR5在突触周围环状区域（定义为突触边缘60纳米范围内）显示出最高的受体密度，随后突触外（60 - 900纳米）受体水平逐渐降低，但两种受体的降低梯度和突触周围池的比例（mGluR1α约为50%；mGluR5约为25%）不同。mGluR1α和mGluR5的分布也与模拟随机分布有显著差异。相比之下，mGluR2在小脑高尔基细胞树突质膜中与谷氨酸能突触没有紧密关联，其相对于突触的分布与膜中的模拟随机分布没有差异。GABA能高尔基细胞的体膜、轴突和突触小体也含有与突触特化无关的免疫反应性mGluR2。在海马CA1区，使用连续切片确定了mGluR5在单个树突棘上免疫颗粒的分布。结果表明，锥体细胞的树突棘在突触周围与突触外mGluR5池的比例方面是异质的，约一半的免疫阳性树突棘缺乏突触周围池。受体分布的定量比较表明，mGluR1α和mGluR5，而非mGluR2，在不同的质膜结构域中高度分隔。每种mGluR亚型的独特分布可能反映了不同细胞类型以及同一细胞不同结构域之间对不同转导和效应机制的需求，并表明受体的精确定位是促进神经元通讯的关键因素。
