Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
J Neurosci. 2011 May 18;31(20):7334-40. doi: 10.1523/JNEUROSCI.0100-11.2011.
Auxiliary proteins modify the biophysical function and pharmacological properties of ionotropic glutamate receptors and likely are important components of receptor signaling complexes in vivo. The neuropilin and tolloid-like proteins (NETO) 1 and NETO2, two closely related CUB domain-containing integral membrane proteins, were identified recently as auxiliary proteins that slowed GluK2a kainate receptor current kinetics without impacting receptor membrane localization. Here we demonstrate that NETO2 profoundly slows the desensitization rate of GluK1 kainate receptors, promotes plasma membrane localization of transfected receptors in heterologous cells and rat hippocampal neurons, and targets GluK1-containing receptors to synapses. Conversely, the closely related protein NETO1 increases the rate of GluK1 receptor desensitization. Incorporation of NETO proteins into kainate receptor-signaling complexes therefore extends the temporal range of receptor gating by over an order of magnitude. The presence of these auxiliary proteins could underlie some of the unusual aspects of kainate receptor function in the mammalian CNS.
辅助蛋白可改变离子型谷氨酸受体的生物物理功能和药理学特性，并且可能是体内受体信号转导复合物的重要组成部分。最近发现神经纤毛蛋白和 tolloid 样蛋白（NETO）1 和 NETO2 是两种密切相关的含 CUB 结构域的完整膜蛋白，它们作为辅助蛋白可减缓 GluK2a 型谷氨酸受体电流动力学，而不影响受体膜定位。在这里，我们证明 NETO2 可显著减缓 GluK1 型谷氨酸受体脱敏的速率，促进转染的受体在异源细胞和大鼠海马神经元中的质膜定位，并将包含 GluK1 的受体靶向突触。相反，密切相关的蛋白 NETO1 增加了 GluK1 受体脱敏的速率。因此，NETO 蛋白整合到谷氨酸受体信号转导复合物中可使受体门控的时间范围延长一个数量级以上。这些辅助蛋白的存在可能是哺乳动物中枢神经系统中谷氨酸受体功能的一些异常方面的基础。
