Fukaya Masahiro, Uchigashima Motokazu, Nomura Sachi, Hasegawa Yuta, Kikuchi Hisaya, Watanabe Masahiko
Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.
Eur J Neurosci. 2008 Nov;28(9):1744-59. doi: 10.1111/j.1460-9568.2008.06495.x.
Upon activation of receptors coupled to the Gq subclass of G proteins, phospholipase C (PLC)beta hydrolyses membrane phospholipid to yield a pair of second messengers, inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. Of four PLCbeta isoforms, PLCbeta1 is transcribed predominantly in the telencephalon and its gene inactivation in mice impairs metabotropic glutamate receptor- and muscarinic acetylcholine receptor-dependent hippocampal oscillations, endocannabinoid production in the hippocampus and barrel formation in the somatosensory cortex. Here we examined cellular and subcellular distributions of PLCbeta1 in adult mouse brains. In the telencephalon, high levels of PLCbeta1 were observed in principal neurons, including pyramidal cells in the cortex and hippocampus, granule cells and mossy cells in the dentate gyrus, and medium spiny neurons in the caudate-putamen, whereas most interneurons had low levels of or were negative for PLCbeta1 and, instead, expressed PLCbeta4. By immunofluorescence, tiny clusters of PLCbeta1 were distributed in somatodendritic compartments of principal neurons and positioned close to those of metabotropic glutamate receptor 5, muscarinic acetylcholine receptor M1 and diacylglycerol lipase-alpha, respectively. Immunoelectron microscopy revealed that PLCbeta1 was often associated with the smooth endoplasmic reticulum, cell membrane or postsynaptic density. In particular, it was highly accumulated at the perisynapse of dendritic spines forming asymmetrical synapses. In the cerebellum, PLCbeta1 was generally low but was enriched in axons and dendrites of basket cells. These results suggest that PLCbeta1 is the key effector in telencephalic principal neurons and cerebellar interneurons. Furthermore, the well-orchestrated molecular arrangement appears to be the anatomical basis for the specificity, efficiency and convergence of the neuronal phosphoinositide signaling system.
当与G蛋白的Gq亚类偶联的受体被激活时，磷脂酶C（PLC）β会水解膜磷脂，产生一对第二信使，即肌醇1,4,5-三磷酸和1,2-二酰基甘油。在四种PLCβ同工型中，PLCβ1主要在端脑中转录，其在小鼠中的基因失活会损害代谢型谷氨酸受体和毒蕈碱型乙酰胆碱受体依赖性海马振荡、海马体内源性大麻素的产生以及体感皮层中的桶状结构形成。在这里，我们研究了成年小鼠大脑中PLCβ1的细胞和亚细胞分布。在端脑中，在主要神经元中观察到高水平的PLCβ1，包括皮层和海马体中的锥体细胞、齿状回中的颗粒细胞和苔藓细胞，以及尾状核-壳核中的中等棘状神经元，而大多数中间神经元的PLCβ1水平较低或为阴性，相反，它们表达PLCβ4。通过免疫荧光，PLCβ1的微小簇分布在主要神经元的树突-体细胞区室中，分别靠近代谢型谷氨酸受体5、毒蕈碱型乙酰胆碱受体M1和二酰基甘油脂肪酶-α的微小簇。免疫电子显微镜显示，PLCβ1通常与光滑内质网、细胞膜或突触后致密物相关。特别是，它高度聚集在形成不对称突触的树突棘的突触周围。在小脑中，PLCβ1一般含量较低，但在篮状细胞的轴突和树突中富集。这些结果表明，PLCβ1是端脑主要神经元和小脑中间神经元中的关键效应器。此外，精心编排的分子排列似乎是神经元磷酸肌醇信号系统特异性、效率和汇聚性的解剖学基础。
