Tmem100 Is a Regulator of TRPA1-TRPV1 Complex and Contributes to Persistent Pain

Hao Jui Weng, Kush N. Patel, Nathaniel A. Jeske, Sonya M. Bierbower, Wangyuan Zou, Vinod Tiwari, Qin Zheng, Zongxiang Tang, Gary C.H. Mo, Yan Wang, Yixun Geng, Jin Zhang, Yun Guan, Armen N. Akopian, Xinzhong Dong

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

TRPA1 and TRPV1 are crucial pain mediators, but how their interaction contributes to persistent pain is unknown. Here, we identify Tmem100 as a potentiating modulator of TRPA1-V1 complexes. Tmem100 is coexpressed and forms a complex with TRPA1 and TRPV1 in DRG neurons. Tmem100-deficient mice show a reduction in inflammatory mechanical hyperalgesia and TRPA1- but not TRPV1-mediated pain. Single-channel recording in a heterologous system reveals that Tmem100 selectively potentiatesTRPA1 activity in a TRPV1-dependent manner. Mechanistically, Tmem100 weakens the association of TRPA1 and TRPV1, thereby releasing the inhibitionof TRPA1 by TRPV1. A Tmem100 mutant, Tmem100-3Q, exerts the opposite effect; i.e., it enhances theassociation of TRPA1 and TRPV1 and strongly inhibits TRPA1. Strikingly, a cell-permeable peptide(CPP) containing the C-terminal sequence ofTmem100-3Q mimics its effect and inhibits persistent pain. Our study unveils a context-dependent modulation of the TRPA1-V1 complex, and Tmem100-3Q CPP is a promising pain therapy.

Original languageEnglish (US)
Pages (from-to)833-846
Number of pages14
JournalNeuron
Volume85
Issue number4
DOIs
StatePublished - Feb 18 2015

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Tmem100 Is a Regulator of TRPA1-TRPV1 Complex and Contributes to Persistent Pain'. Together they form a unique fingerprint.

  • Cite this

    Weng, H. J., Patel, K. N., Jeske, N. A., Bierbower, S. M., Zou, W., Tiwari, V., Zheng, Q., Tang, Z., Mo, G. C. H., Wang, Y., Geng, Y., Zhang, J., Guan, Y., Akopian, A. N., & Dong, X. (2015). Tmem100 Is a Regulator of TRPA1-TRPV1 Complex and Contributes to Persistent Pain. Neuron, 85(4), 833-846. https://doi.org/10.1016/j.neuron.2014.12.065