Postsynaptic assembly induced by neurexin-neuroligin interaction and neurotransmitter
Postsynaptic assembly induced by neurexin-neuroligin interaction and neurotransmitter
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DOI：
10.1073/pnas.0502038102
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发表时间：
2005-04-26
影响因子：
11.1
通讯作者：
Chen, L
中科院分区：
文献类型：
--
作者：
Nam, CI;Chen, L
突触前和突触后分化发生在中枢神经系统神经元之间的轴突接触处。由突触细胞粘附分子 (SynCAM) 和 β-neurexins/neuroligin 介导的突触粘附触发突触前分化。然而，触发突触后分化的信号尚不清楚。在这里，我们报告非神经元细胞中表达的 β-neurexin 诱导海马神经元接触树突中的突触后密度（PSD）-95 聚集。该效应是 β-neurexin 特有的，而其他突触细胞粘附分子（例如 N-cadherin 或 SynCAM）则未观察到该效应。 NMDA 受体，但不是 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯受体 (AMPARS)，被招募到这个 β-neurexin 诱导的 PSD-95 支架上。值得注意的是，在应用谷氨酸或在神经元中表达钙调蛋白激酶 II 的组成型活性形式后，AMPAR 被插入到该支架中。培养神经元中显性失活的 Neuroligin-1 的表达显着降低了 PSD-95 斑点和 AMPAR 簇的大小和密度。此外，这些神经元的兴奋性而非抑制性突触功能受损，证实 PSD-95/neuroligin-1 相互作用参与谷氨酸能突触的突触后组装。这些结果表明，谷氨酸能突触的突触后组装可能是由突触前β-神经毒素启动的，并且谷氨酸释放也是突触成熟所必需的。
Presynaptic and postsynaptic differentiation occurs at axodendritic contacts between CNS neurons. Synaptic adhesion mediated by synaptic cell adhesion molecule (SynCAM) and beta-neurexins/neuroligins triggers presynaptic differentiation. The signals that trigger postsynaptic differentiation are, however, unknown. Here we report that beta-neurexin expressed in nonneuronal cells induced postsynaptic density (PSD)-95 clustering in contacting dendrites of hippocampal neurons. The effect is specific to beta-neurexin and was not observed with other synaptic cell adhesion molecules such as N-cadherin or SynCAM. NMDA receptors, but not alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate receptors (AMPARS), were recruited to this beta-neurexin-induced PSD-95 scaffold. Remarkably, AMPARs were inserted into this scaffold upon glutamate application or expression of a constitutively active form of calmodulin kinase II in neurons. Expression of a dominant-negative neuroligin-1 in cultured neurons markedly reduced the sizes and densities of PSD-95 puncta and AMPAR clusters. In addition, excitatory, but not inhibitory, synaptic functions were impaired in these neurons, confirming that PSD-95/neuroligin-1 interaction is involved in postsynaptic assembly at glutamatergic synapses. These results demonstrate that postsynaptic assembly of the glutamatergic synapse may be initiated by presynaptic beta-neurexin and that glutamate release also is required for maturation of synapses.