Department of Biological Sciences, Pusan National University, Busan, 46241, South Korea.
Department of Anesthesiology, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, 64108, USA.
Mol Neurobiol. 2017 Nov;54(9):7156-7170. doi: 10.1007/s12035-016-0225-4. Epub 2016 Oct 29.
A synaptic pool of extracellular signal-regulated kinases (ERK) controls synaptic transmission, although little is known about its underlying signaling mechanisms. Here, we found that synaptic ERK2 directly binds to postsynaptic metabotropic glutamate receptor 1a (mGluR1a). This binding is direct and the ERK-binding site is located in the intracellular C-terminus (CT) of mGluR1a. Parallel with this binding, ERK2 phosphorylates mGluR1a at a cluster of serine residues in the distal part of mGluR1a-CT. In rat cerebellar neurons, ERK2 interacts with mGluR1a at synaptic sites, and active ERK constitutively phosphorylates mGluR1a under normal conditions. This basal phosphorylation is critical for maintaining adequate surface expression of mGluR1a. ERK is also essential for controlling mGluR1a signaling in triggering distinct postreceptor signaling transduction pathways. In summary, we have demonstrated that mGluR1a is a sufficient substrate of ERK2. ERK that interacts with and phosphorylates mGluR1a is involved in the regulation of the trafficking and signaling of mGluR1.
一个细胞外信号调节激酶（ERK）的突触池控制着突触传递，尽管其潜在的信号机制知之甚少。在这里，我们发现突触 ERK2 直接与突触后代谢型谷氨酸受体 1a（mGluR1a）结合。这种结合是直接的，ERK 结合位点位于 mGluR1a 的细胞内 C 端（CT）。与这种结合平行的是，ERK2 在 mGluR1a-CT 的远端部分的一组丝氨酸残基上磷酸化 mGluR1a。在大鼠小脑神经元中，ERK2 在突触部位与 mGluR1a 相互作用，并且在正常条件下，活性 ERK 持续磷酸化 mGluR1a。这种基础磷酸化对于维持 mGluR1a 的足够表面表达至关重要。ERK 对于控制 mGluR1a 信号转导以触发不同的受体后信号转导途径也是必不可少的。总之，我们已经证明 mGluR1a 是 ERK2 的充分底物。与 mGluR1a 相互作用并磷酸化 mGluR1a 的 ERK 参与 mGluR1 的运输和信号转导的调节。
