Referenced in: none

Automatically associated channels: TRP , TRPA , TRPA1 , TRPV , TRPV1

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

Authors: 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

Journal, date & volume: Neuron, 2015 Feb 18 , 85, 833-46

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25640077

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 potentiates TRPA1 activity in a TRPV1-dependent manner. Mechanistically, Tmem100 weakens the association of TRPA1 and TRPV1, thereby releasing the inhibition of TRPA1 by TRPV1. A Tmem100 mutant, Tmem100-3Q, exerts the opposite effect; i.e., it enhances the association of TRPA1 and TRPV1 and strongly inhibits TRPA1. Strikingly, a cell-permeable peptide (CPP) containing the C-terminal sequence of Tmem100-3Q 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.