Phosphorylation on TRPV4 Serine 824 Regulates Interaction with STIM1

• Published in: The open biochemistry journal Vol. 9; no. 1; pp. 24 - 33
• Main Authors: Shin, Sung H, Lee, Eun J, Chun, Jaesun, Hyun, Sunghee, Kang, Sang S
• Format: Journal Article
• Language: English
• Published: United Arab Emirates Bentham Open 2015
• Subjects: protein-protein interaction; STIM1; phosphorylation; TRPV4; Channel
• ISSN: 1874-091X; 1874-091X
• DOI: 10.2174/1874091X01509010024

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.