红藻氨酸受体(KAR)是介导兴奋性突触传递的谷氨酸受体亚家族,最近发现Neto蛋白是KAR的辅助亚基。然而,Neto蛋白在KARGluK1突触运输中的作用尚不清楚。这里,使用海马CA1锥体神经元作为空背景系统,我们发现GluK1受体本身的表面表达非常有限,并且不针对兴奋性突触。Neto1和Neto2都显著增加GluK1表面表达,并驱动GluK1进入突触。然而,Neto蛋白对GluK1突触靶向的调节与它们在促进表面运输中的作用无关。有趣的是,GluK1被排除在表达AMPA受体的突触之外,并选择性地掺入沉默的突触中。Neto2,而不是Neto1,减缓GluK1停用,而Neto1加速GluK1脱敏,而Neto2减缓脱敏。这些结果为控制KARs特性和突触掺入的Neto辅助亚基建立了关键作用。
Kainate receptors (KARs) are a subfamily of glutamate receptors mediating excitatory synaptic transmission and
Neto proteins are recently identified auxiliary subunits for KARs. However, the roles of
Neto proteins in the synaptic trafficking of KAR GluK1 are poorly understood. Here, using the hippocampal CA1 pyramidal neuron as a null background system we find that surface expression of GluK1 receptor itself is very limited and is not targeted to excitatory synapses. Both Neto1 and Neto2 profoundly increase GluK1 surface expression and also drive GluK1 to synapses. However, the regulation GluK1 synaptic targeting by
Neto proteins is independent of their role in promoting surface trafficking. Interestingly, GluK1 is excluded from synapses expressing AMPA receptors and is selectively incorporated into silent synapses. Neto2, but not Neto1, slows GluK1 deactivation, whereas Neto1 speeds GluK1 desensitization and Neto2 slows desensitization. These results establish critical roles for
Neto auxiliary subunits controlling KARs properties and synaptic incorporation.