title: Identification of a splice variant of mouse TRPA1 that regulates TRPA1 activity.
abstract: Transient receptor potential ankyrin 1 (TRPA1) protein is a nonselective cation channel. Although many studies suggest that TRPA1 is involved in inflammatory and neuropathic pain, its mechanism remains unclear. Here we identify an alternative splice variant of the mouse Trpa1 gene. TRPA1a (full-length) and TRPA1b (splice variant) physically interact with each other and TRPA1b increases the expression of TRPA1a in the plasma membrane. TRPA1a and TRPA1b co-expression significantly increases current density in response to different agonists without affecting their single-channel conductance. Exogenous overexpression of Trpa1b gene in wild-type and TRPA1KO DRG neurons also increases TRPA1a-mediated AITC responses. Moreover, expression levels of Trpa1a and Trpa1b mRNAs change dynamically in two pain models (complete Freund's adjuvant-induced inflammatory pain and partial sciatic nerve ligation-induced neuropathic pain models). These results suggest that TRPA1 may be regulated through alternative splicing under these pathological conditions.
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki, Japan.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Uchida
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001896:Boron Compounds / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003001:Cloning, Molecular; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D015640:Ion Channel Gating / Q000187:drug effects; D017879:Isothiocyanates / Q000494:pharmacology; D051379:Mice; D023421:Models, Animal; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D001896:Boron Compounds; D017879:Isothiocyanates; D012333:RNA, Messenger; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C004471:allyl isothiocyanate; C109986:2-aminoethoxydiphenyl borate; D002211:Capsaicin