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

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 modula...

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Bibliographic Details
Published in:Neuropharmacology 2020-06, Vol.170, p.108046-108046, Article 108046
Main Authors: Luo, Limin, Huang, Min, Zhang, Yu, Wang, Wenying, Ma, Xiaqing, Shi, Haibo, Worley, Paul F., Kim, Dong Kwan, Fedorovich, Sergei V., Jiang, Wei, Xu, Tao
Format: Article
Language:English
Subjects:
Homer
Inflammatory pain
Metabotropic glutamate receptor 5
Phosphorylation
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Summary: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. [Display omitted] •CFA-induced inflammatory pain caused phosphorylation at Ser1126 of mGluR5.•Phosphorylation at Ser1126 of mGluR5 increases mGluR5-Homer interaction in CFA pain.•Mutation at Thr1123 and Ser1126 of mGluR5 alleviated CFA-induced inflammatory pain.
ISSN:0028-3908
1873-7064
DOI:10.1016/j.neuropharm.2020.108046