Neto蛋白对kainate-型谷氨酸受体的突触定位和功能的调节作用

Kainate-型谷氨酸受体，在中枢神经系统的兴奋性神经递质传递中起着重要的作用。突触后膜上的kainate受体的基本功能是被突触前膜释放的谷氨酸分子激活，介导离子进出细胞而改变突触后神经元的兴奋性。Kainate 受体功能的紊乱会导致兴奋性神经毒作用和退行性神经疾病。但是kainate受体如何进入突触膜的过程并不清楚。最近的研究发现，脑内的kainate受体结合有辅助亚基- - Neto家族蛋白，Neto蛋白调节kainate受体的药理特性和动力学。申请人近期的工作（Nature, 2013）发现Neto 蛋白促进kainate受体的突触表达。 Neto是否对kainate 受体突触定位起决定性的作用呢？本研究将综合利用神经电生理，分子生物学的研究方法，从过表达和基因敲除两个方面着重研究Neto蛋白对kainate受体的跨膜转运、突触定位和功能的影响。

Kainate receptors,a type of ionotropic glutamate receptors, play an important role in excitatory neurotransmission in the CNS. Binding glutamate, the postsynaptic kainite receptors are activated, mediate cations flux through membrane and lead to membrane depolarization. Malfunction of kainite receptors results in excitotoxicity and neurodegenarative diseases. However, how kainate receptor traffic to membrane and target to synapses remains elusive. Recent studies demonstrate that Netos, a new family of auxiliary proteins in brain, modulate kainate receptor pharmocological properties and kinetics. Our recent work found that Netos promote kainate receptor synaptic expression (Grager A, Shi Y, et al, 2013). Are Netos required for kainate receptor synaptic targeting? This proposal will use a combination of electrophysiological and molecular techniques to study the role of Netos in membrane trafficking,synaptic targeting and function of kainate receptors. The study might estabolish Netos as new therapeutic targets for neuroexcitatory damages in future.