Synaptic scaffolding molecule is involved in the synaptic clustering of neuroligin
Synaptic scaffolding molecule is involved in the synaptic clustering of neuroligin
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DOI：
10.1016/j.mcn.2004.08.006
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发表时间：
2004-12-01
影响因子：
3.5
通讯作者：
Hata, Y
中科院分区：
文献类型：
--
作者：
Lida, J;Hirabayashi, S;Hata, Y
S-SCAM具有与PSD-95相似的分子组织。它们都与细胞粘附分子神经素相互作用。我们之前报道过β -连环蛋白结合S-SCAM并将其招募到突触。我们在这里用大鼠原代培养的神经元研究了神经胶质素是将S-SCAM招募到突触还是S-SCAM决定了神经胶质素的定位。过表达的神经球蛋白在S-SCAM共表达下形成更大的簇，而在PSD-95共表达下则不形成。过表达的神经胶质素阻断了PSD-95的突触积累，但没有阻断S-SCAM。含有神经脂素结合区的S-SCAM突变体干扰了神经脂素和PSD-95的突触积累，而PSD-95的类似突变体则没有影响。生化研究表明，神经素与S-SCAM和PSD-95通过多种相互作用形成三元配合物。这些发现表明S-SCAM被β -连环蛋白拴在突触上，并诱导神经胶质素的突触积累，随后将PSD-95招募到突触。(C) 2004爱思唯尔公司版权所有。
S-SCAM has a similar molecular organization to PSD-95. Both of them interact with a cell adhesion molecule, neuroligin. We previously reported that beta-catenin binds S-SCAM and recruits it to synapses. We have here examined using rat primary cultured neurons whether neuroligin recruits S-SCAM to synapses or S-SCAM determines the localization of neuroligin. Overexpressed neuroligin formed larger clusters under co-expression of S-SCAM but not of PSD-95. Overexpressed neuroligin blocked synaptic accumulation of PSD-95 but not of S-SCAM. S-SCAM mutant containing the neuroligin-binding region interfered with synaptic accumulation of neuroligin and PSD-95, whereas the similar mutant of PSD-95 had no effect. Biochemical studies revealed that neuroligin forms a ternary complex with S-SCAM and PSD-95 through manifold interactions. These findings imply that S-SCAM is tethered by beta-catenin to synapses and induces synaptic accumulation of neuroligin, which subsequently recruits PSD-95 to synapses. (C) 2004 Elsevier Inc. All rights reserved.