RESEARCH ARTICLE


Phosphorylation on TRPV4 Serine 824 Regulates Interaction with STIM1



Sung H Shin 1, Eun J Lee 1, §, Jaesun Chun 2, Sunghee Hyun 3, Sang S Kang *, 1, §
1 Department of Biology Education, Chungbuk National University, 410 Seongbong Road, Heungdok-gu, Cheongju,Chungbuk, 361-763, Republic of Korea
2 Department of Biology Education, Korea National University of Education, Chongwon,Chungbuk 363-791, Republic of Korea
3 Department of Biomedical Laboratory Science, Eulji University, Daejeon 301-832, Republic of Korea


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© Shin et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Biology Education, Chungbuk National University, Gaeshin-dong, Heungdok-gu, Cheongju, Chungbuk, 361-763, Republic of Korea; Tel: +82 43 261 3278; Fax: +82 43 271 0526; E-mail: jin95324@cbu.ac.kr
§ Both authors contributed equally.


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.

Keywords: Channel, phosphorylation, protein-protein interaction, STIM1, TRPV4.