Disabling phosphorylation at the homer ligand of the metabotropic glutamate receptor 5 alleviates complete Freund's adjuvant-induced inflammatory pain

Limin Luo, Min Huang, Yu Zhang, Wenying Wang, Xiaqing Ma, Haibo Shi, Paul F. Worley, Dong Kwan Kim, Sergei V. Fedorovich, Wei Jiang, Tao Xu

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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 Ser1126 and mGluR5/Homer crosslinking were detected. Mutant mGluR5 that could not be phosphorylated at Thr1123 or Ser1126 was evaluated in inflammatory pain. CFA-induced inflammatory pain resulted in obvious phosphorylation at Ser1126 of mGluR5. Moreover, increased phosphorylation at the Homer-binding motif enhanced crosslinking between mGluR5 and Homer. Mutations at Thr1123 and Ser1126 of mGluR5 blocked the development of CFA-induced inflammatory pain. Overall, our findings showed that disruption of the phosphorylation of mGluR5 Thr1123 and Ser1126 alleviated CFA-induced inflammatory pain.

Original languageEnglish (US)
Article number108046
JournalNeuropharmacology
Volume170
DOIs
StatePublished - Jun 15 2020

Keywords

  • Homer
  • Inflammatory pain
  • Metabotropic glutamate receptor 5
  • Phosphorylation

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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