Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan.
Neurosci Lett. 2013 Jan 15;533:44-9. doi: 10.1016/j.neulet.2012.11.019. Epub 2012 Nov 23.
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.
突触相关蛋白 102（SAP102）和突触后密度蛋白 95（PSD-95）通过 PDZ 结构域与 NMDA 受体结合，并聚集在兴奋性突触后位点，称为突触后密度（PSD）。我们之前报道过，含有不能结合配体的突变 PDZ 结构域的 PSD-95 以降低的效率聚集在突触部位。在这里，我们比较了同一系列全长 SAP102 突变体在海马神经元中的突触聚集情况。出乎意料的是，配体结合缺陷的突变 SAP102 比野生型 SAP102 具有更高的突触定位效率。此外，当 SAP102-PDZ 突变体与 GluN2A 或 GluN2B NMDA 受体亚基共表达时，两个亚基的突触聚集都减少了，尽管突变体被有效地靶向突触。这一发现表明，NMDA 受体与 SAP102 的直接结合参与了 NMDA 受体向突触的有效靶向，而 PDZ 结构域的配体结合对于 SAP102 的突触聚集并不是必需的。
