The postsynaptic scaffold proteins ProSAP1/Shank2 and homer1 are associated with glutamate receptor complexes at rat retinal synapses
The postsynaptic scaffold proteins ProSAP1/Shank2 and homer1 are associated with glutamate receptor complexes at rat retinal synapses
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DOI：
10.1002/cne.20194
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发表时间：
2004-08-02
影响因子：
2.5
通讯作者：
Boeckers, TM
中科院分区：
文献类型：
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作者：
Brandstätter, JH;Dick, O;Boeckers, TM
谷氨酸能突触的突触后密度（PSD）是一种由各种分子组成的大分子复合物，它将不同的谷氨酸受体在空间上组织起来，并将它们连接到相应的下游信号通路和细胞骨架上。最近，一个新的多结构域蛋白家族被发现，称为Shanks或proaps（富含脯氨酸的突触相关蛋白）。它们被认为是谷氨酸能突触PSD的中心接头蛋白，连接不同类型的谷氨酸受体复合物。利用免疫细胞化学、光镜和电镜技术，研究了ProSAP1/Shank2在大鼠视网膜突触的细胞、突触和出生后发育表达。通过双标记实验和共聚焦显微镜，我们分析了ProSAP1/Shank2与谷氨酸能、甘氨酸能和γ -氨基丁酸（GABA）能突触特异性蛋白的关系，以及与含有n -甲基- d -天冬氨酸受体[95-kDa突触后密度蛋白（PSD-95）]、I组代谢型谷氨酸受体（Homer1）、n -甲基- d -天冬氨酸受体（PSD-95）的psd结构和功能组织相关的蛋白的关系。α -氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体[谷氨酸受体相互作用蛋白（GRIP）]。ProSAP1/Shank2在光感受器和双极细胞的谷氨酸能带突触突触后存在，而在甘氨酸能和gaba能无分泌细胞突触中不存在。双标记实验显示ProSAP1/Shank2与Homer1和PSD-95共定位率高，与GRIP共定位率低。这些数据表明ProSAP1/Shank2在不同谷氨酸能视网膜突触的psd中起组织者作用。(C) 2004 Wiley-Liss, Inc。
The postsynaptic density (PSD) at glutamatergic synapses is a macromolecular complex of various molecules that organize the different glutamate receptors spatially and link them to their appropriate downstream signaling pathways and to the cytoskeleton. Recently, a new family of multidomain proteins called Shanks or ProSAPs (proline-rich synapse-associated proteins) has been identified. They are suggested to be central adaptor proteins of the PSD of glutamatergic synapses, bridging different types of glutamate receptor complexes. With immunocytochemistry and light and electron microscopy, we examined the cellular, synaptic, and postnatal developmental expression of ProSAP1/Shank2 at the synapses of rat retina. With double-labeling experiments and confocal microscopy, we analyzed the association of ProSAP1/Shank2 with proteins specific for glutamatergic, glycinergic, and gamma-aminobutyric acid (GABA)ergic synapses and with proteins known to be involved in the structural and functional organization of PSDs containing N-methyl-D-aspartate receptors [95-kDa postsynaptic density protein (PSD-95)], group I metabotropic glutamate receptors (Homer1), and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors [glutamate receptor-interacting protein (GRIP)]. ProSAP1/Shank2 was present postsynaptically at the glutamatergic ribbon synapses of photoreceptor and bipolar cells, and it was absent from glycinergic and GABAergic amacrine cell synapses. The double-labeling experiments revealed a high rate of colocalization of ProSAP1/Shank2 with Homer1 and PSD-95, and little colocalization with GRIP. These data suggest that ProSAP1/Shank2 acts as an organizer at PSDs of different glutamatergic retinal synapses. (C) 2004 Wiley-Liss, Inc.