Interaction Domains for TRPV1 Homomer and TRPV1-TRPA1 Heteromer

The somatosensory system includes highly specialized “pain sensing” sensory neurons, termed nociceptors. The initiation of “pain sensing” begins at the channel level. Thus, TRPV1 and TRPA1 belonging to the TRP super family of channels on nociceptors and detect noxious stimuli including chemical, heat, cold and mechanical insult. Functions of TRPA1 and TRPV1 channels are regulated in a variety of ways. We recently demonstrated that TRPA1 and TRPV1 channels can control each other’s functions via interaction in sensory neurons (Akopian et. al., 2007; Akopian et. al., 2008; Salas et al., 2009 and Staruschenko et al., 2010). This type of regulation allows great flexibility and specificity for the pain pathway in regulation of functions for both channels. To fully examine this lane in regulation of TRPA1 and TRPV1 activities, it is necessary to identify domain(s) involved in TRPV1-TRPV1 (homomer) and TRPA1-TRPV1 (heteromer) interactions. Accordingly, in the present study we propose to identify TRPV1 domain(s) involved in homomeric (TRPV1-TRPV1) and heteromeric (TRPA1-TRPV1) interactions. We evaluated three parameters which are characteristics for interactions between channels: a) modulations of mustard oil responses by co-expression of TRPA1 with wild-type and mutant TRPV1 constructs containing several deletions; b) rescue of impaired capsaicin responses of mutant TRPV1 constructs by co-expression with the TRPA1 channel; and c) co-immunoprecipitation of wild-type TRPV1 or TRPA1 with mutated TRPV1. Our results indicate that TRPV1-TRPV1 and TRPA1-TRPV1 could recruit different interaction domain(s). Altogether, this finding could allow us to manipulate activity of both channels without impairing baseline function of TRPA1 and TRPV1 subunits.