Department of Anesthesiology, Affiliated Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200233, China.
Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China; Department of Otolaryngology, Affiliated Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200233, China.
Neuropharmacology. 2020 Jun 15;170:108046. doi: 10.1016/j.neuropharm.2020.108046. Epub 2020 Mar 7.
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 and mGluR5/Homer crosslinking were detected. Mutant mGluR5 that could not be phosphorylated at Thr or Ser was evaluated in inflammatory pain. CFA-induced inflammatory pain resulted in obvious phosphorylation at Ser of mGluR5. Moreover, increased phosphorylation at the Homer-binding motif enhanced crosslinking between mGluR5 and Homer. Mutations at Thr and Ser of mGluR5 blocked the development of CFA-induced inflammatory pain. Overall, our findings showed that disruption of the phosphorylation of mGluR5 Thr and Ser alleviated CFA-induced inflammatory pain.
代谢型谷氨酸受体 5（mGluR5）已被报道有助于炎症性疼痛。细胞内 C 端结构域具有 Homer 结合基序，可以形成 mGluR5/Homer 复合物。mGluR5 在 Homer 结合域的磷酸化增强了 mGluR5/Homer 的相互作用，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。我们旨在评估 CFA 诱导的 Homer 结合域 mGluR5 磷酸化对 mGluR5/Homer 相互作用的影响。von-Frey 纤维和热潜伏期用于监测炎症性疼痛的发展。检测脊髓 mGluR5 在 Ser 的磷酸化和 mGluR5/Homer 交联。评估不能在 Thr 或 Ser 磷酸化的突变型 mGluR5 在炎症性疼痛中的作用。CFA 诱导的炎症性疼痛导致 mGluR5 在 Ser 明显磷酸化。此外，Homer 结合基序的磷酸化增加增强了 mGluR5 和 Homer 之间的交联。mGluR5 的 Thr 和 Ser 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，破坏 mGluR5 Thr 和 Ser 的磷酸化减轻了 CFA 诱导的炎症性疼痛。
