Synaptic scaffolding molecule (S‐SCAM) membrane‐associated guanylate kinase with inverted organization (MAGI)‐2 is associated with cell adhesion molecules at inhibitory synapses in rat hippocampal neurons
Synaptic scaffolding molecule (S‐SCAM) membrane‐associated guanylate kinase with inverted organization (MAGI)‐2 is associated with cell adhesion molecules at inhibitory synapses in rat hippocampal neurons
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DOI：
10.1111/j.1471-4159.2006.04170.x
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发表时间：
2007-01
影响因子：
4.7
通讯作者：
Kazutaka Sumita;Y. Sato;Junko Iida;Akira Kawata;Mamiko Hamano;S. Hirabayashi;Kikuo Ohno;E. Peles;Y. Hata
中科院分区：
文献类型：
--
作者：
Kazutaka Sumita;Y. Sato;Junko Iida;Akira Kawata;Mamiko Hamano;S. Hirabayashi;Kikuo Ohno;E. Peles;Y. Hata
突触支架分子（Synaptic scaffolding molecule，S-SCAM）是一种突触蛋白，含有五个或六个PSD-95/Discs large/ZO-1（PDZ），一个鸟苷酸激酶和两个WW结构域。它与NMDA受体亚单位、神经连接素和β-连环蛋白相互作用，并参与神经连接素在兴奋性突触的积累。在这项研究中，我们已经证明了S-SCAM定位于大鼠原代培养海马神经元的抑制性突触。我们已经确定β-肌营养不良聚糖（β-DG）作为抑制性突触处S-SCAM的结合伴侣。S-SCAM的WW结构域与β-DG的三个序列结合。我们还发现，S-SCAM可以与神经连接素2相互作用，已知神经连接素2仅定位于抑制性突触。S-SCAM的WW结构域和第二PDZ结构域参与与神经配素2的相互作用。β-DG、neuroligin 2和S-SCAM在体外形成三方复合物。在来自大鼠脑的抗β-DG抗体的免疫沉淀物中检测到神经配素2。S-SCAM、β-DG和neuroligin 2在大鼠海马神经元中部分共定位。这些数据表明，S-SCAM在抑制性突触中与β-DG和神经连接素2相关，并作为肌营养不良蛋白糖蛋白复合物和神经连接素-神经连接素复合物之间的接头发挥作用。
Synaptic scaffolding molecule (S‐SCAM) is a synaptic protein, which harbors five or six PSD‐95/Discs large/ZO‐1 (PDZ), a guanylate kinase and two WW domains. It interacts with NMDA receptor subunits, neuroligin and β‐catenin, and is involved in the accumulation of neuroligin at excitatory synapses. In this study, we have demonstrated S‐SCAM is localized at inhibitory synapses in rat primary cultured hippocampal neurons. We have identified β‐dystroglycan (β‐DG) as a binding partner for S‐SCAM at inhibitory synapses. WW domains of S‐SCAM bind to three sequences of β‐DG. We have also revealed that S‐SCAM can interact with neuroligin 2, which is known to be exclusively localized at inhibitory synapses. The WW domains and the second PDZ domain of S‐SCAM are involved in the interaction with neuroligin 2. β‐DG, neuroligin 2 and S‐SCAM form a tripartite complex in vitro. Neuroligin 2 is detected in the immunoprecipitates by anti‐β‐DG antibody from rat brain. S‐SCAM, β‐DG and neuroligin 2 are partially co‐localized in rat hippocampal neurons. These data suggest that S‐SCAM is associated with β‐DG and neuroligin 2 at inhibitory synapses, and functions as a linker between the dystrophin glycoprotein complex and the neurexin–neuroligin complex.