Zhang Wei, St-Gelais Fannie, Grabner Chad P, Trinidad Jonathan C, Sumioka Akio, Morimoto-Tomita Megumi, Kim Kwang S, Straub Christoph, Burlingame Alma L, Howe James R, Tomita Susumu
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.
Neuron. 2009 Feb 12;61(3):385-96. doi: 10.1016/j.neuron.2008.12.014.
Glutamate receptors play major roles in excitatory transmission in the vertebrate brain. Among ionotropic glutamate receptors (AMPA, kainate, NMDA), AMPA receptors mediate fast synaptic transmission and require TARP auxiliary subunits. NMDA receptors and kainate receptors play roles in synaptic transmission, but it remains uncertain whether these ionotropic glutamate receptors also have essential subunits. Using a proteomic screen, we have identified NETO2, a brain-specific protein of unknown function, as an interactor with kainate-type glutamate receptors. NETO2 modulates the channel properties of recombinant and native kainate receptors without affecting trafficking of the receptors and also modulates kainate-receptor-mediated mEPSCs. Furthermore, we found that kainate receptors regulate the surface expression of NETO2 and that NETO2 protein levels and surface expression are decreased in mice lacking the kainate receptor GluR6. The results show that NETO2 is a kainate receptor subunit with significant effects on glutamate signaling mechanisms in brain.
谷氨酸受体在脊椎动物大脑的兴奋性传递中起主要作用。在离子型谷氨酸受体（AMPA、海人藻酸、NMDA）中，AMPA受体介导快速突触传递，并且需要TARP辅助亚基。NMDA受体和海人藻酸受体在突触传递中发挥作用，但这些离子型谷氨酸受体是否也具有必需亚基仍不确定。通过蛋白质组学筛选，我们鉴定出一种功能未知的脑特异性蛋白NETO2，它是海人藻酸型谷氨酸受体的相互作用蛋白。NETO2调节重组和天然海人藻酸受体的通道特性，而不影响受体的转运，并且还调节海人藻酸受体介导的微小兴奋性突触后电流（mEPSCs）。此外，我们发现海人藻酸受体调节NETO2的表面表达，并且在缺乏海人藻酸受体GluR6的小鼠中，NETO2蛋白水平和表面表达降低。结果表明，NETO2是一种海人藻酸受体亚基，对大脑中的谷氨酸信号传导机制有显著影响。
