title: Mutation of a putative S-nitrosylation site of TRPV4 protein facilitates the channel activates.
abstract: The transient receptor potential vanilloid 4 (TRPV4) cation channel, a member of the TRP vanilloid subfamily, is expressed in a broad range of tissues. Nitric oxide (NO) as a gaseous signal mediator shows a variety of important biological effects. In many instances, NO has been shown to exhibit its activities via a protein S-nitrosylation mechanism in order to regulate its protein functions. With functional assays via site-directed mutagenesis, we demonstrate herein that NO induces the S-nitrosylation of TRPV4 Ca(2+) channel on the Cys(853) residue, and the S-nitrosylation of Cys(853) reduced its channel sensitivity to 4-α phorbol 12,13-didecanoate and the interaction between TRPV4 and calmodulin. A patch clamp experiment and Ca(2+) image analysis show that the S-nitrosylation of Cys(853) modulates the TRPV4 channel as an inhibitor. Thus, our data suggest a novel regulatory mechanism of TRPV4 via NO-mediated S-nitrosylation on its Cys(853) residue.
authors.affiliation: Department of Pre-medicine, Eulji University School of Medicine, Daejeon 301-832, Republic of Korea.
authors.forename: Eun Jeoung
authors.initials: EJ
authors.lastname: Lee
authors.forename: Sung Hwa
authors.initials: SH
authors.lastname: Shin
authors.forename: Sunghee
authors.initials: S
authors.lastname: Hyun
authors.forename: Jaesun
authors.initials: J
authors.lastname: Chun
authors.forename: Sang Sun
authors.initials: SS
authors.lastname: Kang