Block of kainate receptor desensitization uncovers a key trafficking checkpoint
Block of kainate receptor desensitization uncovers a key trafficking checkpoint
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DOI：
10.1016/j.neuron.2006.12.006
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发表时间：
2006-12-21
期刊：
影响因子：
16.2
通讯作者：
Stern-Bach, Yael
中科院分区：
文献类型：
--
作者：
Priel, Avi;Selak, Sanja;Stern-Bach, Yael
来自AMPA和海藻酸盐亚型的离子型谷氨酸受体的突出特征是它们对谷氨酸的深度脱敏作用，响应谷氨酸 - 一种被认为保护神经元免受过度兴奋的过程。在AMPA受体中，众所周知，脱敏是由相邻亚基的激动剂结合域之间形成的界面的重排。但是，目前尚不清楚该机制如何适用于海藻酸盐受体。在这里，我们表明结合结构域二聚体的稳定通过产生分子间二硫键显然阻塞了海藻酸盐受体GlUR6的脱敏。该结果在AMPA和海藻酸盐受体中建立了一种共同的脱敏机制。然而，令人惊讶的是，这些非敏感突变体的表面表达大大降低，不取决于通道活性。因此，除了它在突触中的作用外，我们现在提出了在控制谷氨酸受体成熟和运输中脱敏的细胞内作用。
A prominent feature of ionotropic glutamate receptors from the AMPA and kainate subtypes is their profound desensitization in response to glutamate-a process thought to protect the neuron from overexcitation. In AMPA receptors, it is well established that desensitization results from rearrangements of the interface formed between agonist-binding domains of adjacent subunits; however, it is unclear how this mechanism applies to kainate receptors. Here we show that stabilization of the binding domain dimer by the generation of intermolecular disulfide bonds apparently blocked desensitization of the kainate receptor GluR6. This result establishes a common desensitization mechanism in both AMPA and kainate receptors. Surprisingly, however, surface expression of these nondesensitizing mutants was drastically reduced and did not depend on channel activity. Therefore, in addition to its role at the synapse, we now propose an intracellular role for desensitization in controlling maturation and trafficking of glutamate receptors.