title: Phosphorylation on TRPV4 Serine 824 Regulates Interaction with STIM1.
abstract: The TRPV4 cation channel, a member of the TRP vanilloid subfamily, is expressed in a broad range of tissues where it participates in the generation of a Ca2+ signal and/or depolarization of membrane potential. Here, we identified stromal interaction molecule 1 precursor (STIM1) as an auxiliary protein of this epithelial Ca2+channel using confocal microscopy analysis and GST pull-down assay. The STIM1 protein associates specifically with the C-terminal tail of TRPV4 to form a complex. In previous reports, we demonstrated that the serine824 residue of TRPV4 is one of the target phosphorylation sites of serum/glucocorticoid regulated kinase 1 (SGK1). In this report we further identified the role of serine 824 phosphorylation. The TRPV4 mutant S824D (not S824A) exhibited a diminished capacity to bind STIM1. Using GST pull-down and co-immunoprecipitation assays, we demonstrated that STIM1 is part of the TRPV4 protein complex. Our observations clearly suggest that the formation of a complex between TRPV4 and STIM1 and its plasma membrane localization are regulated through phosphorylation of serine824 of TRPV4, and that the STIM1-TRPV4 complex plays crucial roles in routing TRPV4 to the plasma membrane from the endoplasmic reticulum and in maintaining its function.
authors.affiliation: Department of Biology Education, Chungbuk National University, 410 Seongbong Road, Heungdok-gu, Cheongju,Chungbuk, 361-763, Republic of Korea.
authors.forename: Sung H
authors.initials: SH
authors.lastname: Shin
authors.affiliation: Department of Biology Education, Chungbuk National University, 410 Seongbong Road, Heungdok-gu, Cheongju,Chungbuk, 361-763, Republic of Korea.
authors.forename: Eun J
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Biology Education, Korea National University of Education, Chongwon,Chungbuk 363-791, Republic of Korea.
authors.forename: Jaesun
authors.initials: J
authors.lastname: Chun
authors.affiliation: Department of Biomedical Laboratory Science, Eulji University, Daejeon 301-832, Republic of Korea.
authors.forename: Sunghee
authors.initials: S
authors.lastname: Hyun
authors.affiliation: Department of Biology Education, Chungbuk National University, 410 Seongbong Road, Heungdok-gu, Cheongju,Chungbuk, 361-763, Republic of Korea.
authors.forename: Sang S
authors.initials: SS
authors.lastname: Kang
keywords: Channel; STIM1; TRPV4; phosphorylation; protein-protein interaction