Neto auxiliary proteins control both the trafficking and biophysical properties of the kainate receptor GluK1
Neto auxiliary proteins control both the trafficking and biophysical properties of the kainate receptor GluK1
复制标题
Neto 辅助蛋白控制红藻氨酸受体 GluK1 的运输和生物物理特性。
DOI：
10.7554/elife.11682
复制
发表时间：
2015-12-31
期刊：
影响因子：
7.7
通讯作者：
Nicoll, Roger A.
中科院分区：
文献类型：
--
作者：
Sheng, Nengyin;Shi, Yun S.;Nicoll, Roger A.
红藻氨酸受体（KARs）是谷氨酸受体的一个亚家族，介导兴奋性突触传递，Neto蛋白是最近鉴定的KARs的辅助亚基。然而，Neto蛋白在KAR GluK 1突触运输中的作用尚不清楚。在这里，使用海马CA1区锥体神经元作为一个零背景系统，我们发现，表面表达的GluK1受体本身是非常有限的，并不针对兴奋性突触。Neto1和Neto2都显著增加GluK1表面表达，并将GluK1驱动到突触。然而，Neto蛋白调节GluK1突触靶向作用与其促进表面转运的作用无关。有趣的是，GluK1被排除在表达AMPA受体的突触之外，并被选择性地纳入沉默突触。Neto 2（而不是Neto 1）减缓了GluK 1的失活，而Neto 1加速了GluK 1的脱敏，而Neto 2则减缓了脱敏。这些结果确立了Neto辅助亚基控制KARs特性和突触掺入的关键作用。
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.