Spinophilin negatively controlled the function of transient receptor potential vanilloid 1 in dorsal root ganglia neurons of mice

Protein phosphatase-1 (PP1) is ubiquitously distributed in the nervous system and catalyzes the dephosphorylation of numerous substrates. The specificity and efficacy of PP1-mediated dephosphorylation depend on scaffolding proteins that anchor PP1 to the close vicinity of substrates. Spinophilin is...

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Published in:European journal of pharmacology 2019-11, Vol.863, p.172700-172700, Article 172700
Main Authors: Guo, Zhen, Li, Hu-Ling, Cao, Zheng, Suo, Zhan-Wei, Yang, Xian, Hu, Xiao-Dong
Format: Article
Language:English
Subjects:
Animals
Cell Membrane - metabolism
Dorsal root ganglia
Ganglia, Spinal - cytology
Gene Expression Regulation
Inflammatory pain
Male
Mice
Mice, Inbred C57BL
Microfilament Proteins - metabolism
Nerve Tissue Proteins - metabolism
Neurons - cytology
Neurons - metabolism
Phosphorylation
Protein phosphatase-1
Protein Transport
Spinophilin
Time Factors
Transient receptor potential vanilloid 1
TRPV Cation Channels - metabolism
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Summary:Protein phosphatase-1 (PP1) is ubiquitously distributed in the nervous system and catalyzes the dephosphorylation of numerous substrates. The specificity and efficacy of PP1-mediated dephosphorylation depend on scaffolding proteins that anchor PP1 to the close vicinity of substrates. Spinophilin is one of the scaffolding proteins which are able to direct PP1 into postsynaptic density and regulate the synaptic transmission and plasticity. Here we found that spinophilin was enriched in dorsal root ganglia (DRG) neurons and engaged in the modification of nociceptive signaling processing. Disturbing spinophilin/PP1 interaction in DRG neurons led to the enhanced sensitivity of mice to heat and mechanical stimuli. The transient receptor potential vanilloid 1 (TRPV1) was identified as an important target for spinophilin modification. Our data showed that spinophilin physically interacted with TRPV1 and facilitated PP1 dephosphorylation of TRPV1 at Ser502. Disruption of spinophilin/PP1 complex enhanced Ser502 phosphorylation and boosted TRPV1 expression on plasma membrane. Peripheral inflammation induced by formalin disturbed spinophilin/PP1 interaction, which removed PP1-mediated inhibition and caused a marked increase of TRPV1 phosphorylation. Viral expression of wild-type spinophilin in DRG neurons repressed TRPV1 phosphorylation and alleviated formalin-induced inflammatory pain. These data suggested that spinophilin/PP1 complex negatively controlled TRPV1 function in DRG neurons.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2019.172700