Ligand binding of PDZ domains has various roles in the synaptic clustering of SAP102 and PSD-95
Ligand binding of PDZ domains has various roles in the synaptic clustering of SAP102 and PSD-95
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DOI：
10.1016/j.neulet.2012.11.019
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发表时间：
2013-01
影响因子：
2.5
通讯作者：
Keiichiro Minatohara;Shōgo Ichikawa;Tatsuya Seki;Y. Fujiyoshi;T. Doi
中科院分区：
文献类型：
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作者：
Keiichiro Minatohara;Shōgo Ichikawa;Tatsuya Seki;Y. Fujiyoshi;T. Doi
突触相关蛋白102（SAP 102）和突触后密度-95（PSD-95）通过PDZ结构域与NMDA受体结合，并聚集在称为突触后密度（PSD）的兴奋性突触后位点。我们以前报道，PSD-95含有突变的PDZ域不能配体结合聚集在突触位点的效率降低。在这里，我们比较了海马神经元中相同系列的全长SAP 102突变体的突触簇。出乎意料的是，配体结合缺陷突变体SAP 102显示出比野生型SAP 102更有效的突触定位。此外，当SAP 102-PDZ突变体与GluN 2A或GluN 2B NMDA受体亚基共表达时，两种亚基均显示突触聚集减少，尽管突变体有效地靶向突触。这一发现表明，NMDA受体与SAP 102的直接结合参与了NMDA受体对突触的有效靶向，而PDZ结构域的配体结合对于SAP 102的突触聚集不是必需的。
Synapse-associated protein 102 (SAP102) and postsynaptic density-95 (PSD-95) bind to NMDA receptors through PDZ domains and cluster at excitatory postsynaptic sites called postsynaptic densities (PSD). We previously reported that PSD-95 containing mutated PDZ domains incapable of ligand binding clustered at synaptic sites with reduced efficiency. Here, we compared the synaptic clustering of the same series of full-length SAP102 mutants in hippocampal neurons. Unexpectedly, ligand-binding deficient mutant SAP102 showed more efficient synaptic localization than wild-type SAP102. Further, when SAP102-PDZ mutants were co-expressed with either the GluN2A or GluN2B NMDA receptor subunit, both subunits showed decreased synaptic clustering, although the mutants were efficiently targeted to the synapses. This finding suggests that direct binding of NMDA receptors with SAP102 is involved in the efficient targeting of NMDA receptors to the synapses, whereas ligand binding of the PDZ domains is not essential for the synaptic clustering of SAP102.