A novel multiple PDZ domain-containing molecule interacting with N-methyl-D-aspartate receptors and neuronal cell adhesion proteins
A novel multiple PDZ domain-containing molecule interacting with N-methyl-D-aspartate receptors and neuronal cell adhesion proteins
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DOI：
10.1074/jbc.273.33.21105
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发表时间：
1998-08-14
影响因子：
4.8
通讯作者：
Takai, Y
中科院分区：
文献类型：
--
作者：
Hirao, K;Hata, Y;Takai, Y
在突触连接处，突触前膜和突触后膜通过细胞粘附连接，并且具有用于专门功能的不同结构。突触前膜具有快速释放神经递质的机制，突触后膜具有神经递质受体簇，突触连接组装的分子机制尚不清楚。先驱性研究将突触后密度（PSD）-95/SAP90鉴定为维持突触连接结构的原型突触支架蛋白。PSD-95/SAP 90属于膜相关鸟苷酸激酶家族，并通过PDZ结构域结合N-甲基-D-天冬氨酸受体、钾通道和神经连接素，并通过鸟苷酸激酶（GK）结构域结合GKAP/SAPAP/DAP。我们在这里进行了酵母双杂交筛选SAPAP相互作用的分子，并确定了一种新的蛋白质，具有膜相关的鸟苷酸激酶的反向结构与NH 2-末端GK样结构域，其次是两个WW和五个PDZ结构域。它通过GH样结构域结合SAPAP，通过PDZ结构域结合NMDA受体和神经配蛋白。我们将这种蛋白命名为S-SCAM（synaptic scaffolding molecule），因为S-SCAM可以在突触连接处组装受体和细胞粘附蛋白。
At synaptic junctions, pre- and postsynaptic membranes are connected by cell adhesion and have distinct structures for specialized functions. The presynaptic membranes have a machinery for fast neurotransmitter release, and the postsynaptic membranes have clusters of neurotransmitter receptors, The molecular mechanism of the assembly of synaptic junctions is not yet clear. Pioneering studies identified postsynaptic density (PSD)-95/SAP90 as a prototypic synaptic scaffolding protein to maintain the structure of synaptic junctions. PSD-95/SAP90 belongs to a family of membrane-associated guanylate kinases and binds N-methyl-D-aspartate receptors, potassium channels, and neuroligins through the PDZ domains and GKAP/SAPAP/DAP through the guanylate kinase (GK) domain. We performed here a yeast two-hybrid screening for SAPAP-interacting molecules and identified a novel protein that has an inverse structure of membrane-associated guanylate kinases with an NH2-terminal GK-like domain followed by two WW and five PDZ domains. It binds SAPAP through the GH-like domain and NMDA receptors and neuroligins through the PDZ domains. We named this protein S-SCAM (synaptic scaffolding molecule) because S-SCAM may assemble receptors and cell adhesion proteins at synaptic junctions.