Disabling phosphorylation at the homer ligand of the metabotropic glutamate receptor 5 alleviates complete Freund's adjuvant-induced inflammatory pain
Disabling phosphorylation at the homer ligand of the metabotropic glutamate receptor 5 alleviates complete Freund's adjuvant-induced inflammatory pain
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禁用代谢型谷氨酸受体 5 的 homer 配体的磷酸化可减轻完全弗氏佐剂引起的炎症疼痛
DOI：
10.1016/j.neuropharm.2020.108046
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发表时间：
2020-06-15
影响因子：
4.7
通讯作者：
Xu, Tao
中科院分区：
文献类型：
--
作者：
Luo, Limin;Huang, Min;Xu, Tao
据报道，代谢性谷氨酸受体5 （mGluR5）与炎症性疼痛有关。胞内c端结构域有一个Homer-binding基序，可以形成mGluR5/Homer复合物。mGluR5在Homer结合域的磷酸化增强了mGluR5/Homer相互作用并调节细胞内信号转导。然而，这种相互作用的特征在炎症性疼痛中尚未完全阐明。我们的目的是评估cfa诱导的mGluR5在Homer结合域磷酸化对mGluR5/Homer相互作用的影响。冯弗雷丝和热潜伏期用于监测炎症性疼痛的发展。检测脊髓mGluR5在Ser（1126）位点磷酸化和mGluR5/Homer交联。不能磷酸化Thr（1123）或Ser（1126）的mGluR5突变体在炎症性疼痛中被评估。cfa诱导的炎症性疼痛导致mGluR5丝氨酸（1126）位点明显磷酸化。此外，Homer结合基序磷酸化的增加增强了mGluR5和Homer之间的交联。mGluR5的Thr（1123）和Ser（1126）突变阻断了cfa诱导的炎症性疼痛的发展。总的来说，我们的研究结果表明，mGluR5 Thr（1123）和Ser（1126）磷酸化的破坏减轻了cfa诱导的炎症性疼痛。
Metabotropic glutamate receptor 5 (mGluR5) has been reported to contribute to inflammatory pain. The intracellular C-terminal domain has a Homer-binding motif that can form an mGluR5/Homer complex. Phosphorylation of mGluR5 at the Homer binding domain enhances the mGluR5/Homer interaction and modulates intracellular signal transduction. However, the characteristics of this interaction have not been fully elucidated in inflammatory pain. We aimed to evaluate the effects of CFA-induced phosphorylation of mGluR5 at the Homer binding domain on the mGluR5/Homer interaction. Von-frey filaments and thermal latency were used to monitor the development of inflammatory pain. Spinal mGluR5 phosphorylation at Ser(1126) and mGluR5/Homer crosslinking were detected. Mutant mGluR5 that could not be phosphorylated at Thr(1123) or Ser(1126) was evaluated in inflammatory pain. CFA-induced inflammatory pain resulted in obvious phosphorylation at Ser(1126) of mGluR5. Moreover, increased phosphorylation at the Homer-binding motif enhanced crosslinking between mGluR5 and Homer. Mutations at Thr(1123) and Ser(1126) of mGluR5 blocked the development of CFA-induced inflammatory pain. Overall, our findings showed that disruption of the phosphorylation of mGluR5 Thr(1123) and Ser(1126) alleviated CFA-induced inflammatory pain.