Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine - Sorbonne Université
Journal Articles eLife Year : 2021

Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine

Jin Wang
  • Function : Author
Xin Wei
  • Function : Author
  • PersonId : 772620
  • IdRef : 181647419
Juan Hu
  • Function : Author
Yue Gao
  • Function : Author
Peng Cao
  • Function : Author
Zhengyu Cao
  • Function : Author
Ye Yu
  • Function : Author
Dongdong Li
Jing Yao
  • Function : Author
  • PersonId : 1092201

Abstract

The multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted Syndrome in human. We here report that mouse and human TRPV3 channel is targeted by the clinical medication dyclonine that exerts a potent inhibitory effect. Accordingly, dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. At the single-channel level, dyclonine inhibited TRPV3 open probability but not the unitary conductance. By molecular simulations and mutagenesis, we further uncovered key residues in TRPV3 pore region that could toggle the inhibitory efficiency of dyclonine. The functional and mechanistic insights obtained on dyclonine-TRPV3 interaction will help to conceive updated therapeutics for skin inflammation.
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Dates and versions

hal-03204408 , version 1 (21-04-2021)

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Qiang Liu, Jin Wang, Xin Wei, Juan Hu, Conghui Ping, et al.. Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine. eLife, 2021, 10, pp.e68128. ⟨10.7554/eLife.68128⟩. ⟨hal-03204408⟩
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