IP3 sensitizes TRPV4 channel to the mechano- and osmotransducing messenger 5'-6'-epoxyeicosatrienoic acid

Fernandes, Jacqueline; Lorenzo, Ivan M.; Andrade, Yaniré N.; Garcia-Elias Heras, Anna; Serra Pascual, Selma A., 1981-; Fernández-Fernández, José Manuel, 1967-; Valverde, M. A. (Miguel Ángel), 1963-

IP3 sensitizes TRPV4 channel to the mechano- and osmotransducing messenger 5'-6'-epoxyeicosatrienoic acid

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dc.contributor.author Fernandes, Jacquelineca
dc.contributor.author Lorenzo, Ivan M.ca
dc.contributor.author Andrade, Yaniré N.ca
dc.contributor.author Garcia-Elias Heras, Annaca
dc.contributor.author Serra Pascual, Selma A., 1981-ca
dc.contributor.author Fernández-Fernández, José Manuel, 1967-ca
dc.contributor.author Valverde, M. A. (Miguel Ángel), 1963-ca
dc.date.accessioned 2016-01-21T15:43:22Z
dc.date.available 2016-01-21T15:43:22Z
dc.date.issued 2008
dc.description.abstract Mechanical and osmotic sensitivity of the transient receptor potential vanilloid 4 (TRPV4) channel depends on phospholipase A(2) (PLA(2)) activation and the subsequent production of the arachidonic acid metabolites, epoxyeicosatrienoic acid (EET). We show that both high viscous loading and hypotonicity stimuli in native ciliated epithelial cells use PLA(2)-EET as the primary pathway to activate TRPV4. Under conditions of low PLA(2) activation, both also use extracellular ATP-mediated activation of phospholipase C (PLC)-inositol trisphosphate (IP(3)) signaling to support TRPV4 gating. IP(3), without being an agonist itself, sensitizes TRPV4 to EET in epithelial ciliated cells and cells heterologously expressing TRPV4, an effect inhibited by the IP(3) receptor antagonist xestospongin C. Coimmunoprecipitation assays indicated a physical interaction between TRPV4 and IP(3) receptor 3. Collectively, our study suggests a functional coupling between plasma membrane TRPV4 channels and intracellular store Ca(2+) channels required to initiate and maintain the oscillatory Ca(2+) signal triggered by high viscosity and hypotonic stimuli that do not reach a threshold level of PLA(2) activation.ca
dc.description.sponsorship This work was supported by grants from the Spanish Ministries of Education and Science (SAF2006-04973 and SAF2006-13893-C02-02), and Health (Fondo de Investigación Sanitaria, Red HERACLES RD06/0009), the Generalitat de Catalunya (SGR05-266), and Fundació la Marató de TV3 (061331). J.M. Fernández-Fernández is a Ramón y Cajal Fellow.
dc.format.mimetype application/pdfca
dc.identifier.citation Fernandes J, Lorenzo IM, Andrade YN, Garcia-Elias A, Serra SA, Fernández-Fernández JM et al. IP3 sensitizes TRPV4 channel to the mechano- and osmotransducing messenger 5'-6'-epoxyeicosatrienoic acid. Journal of cell biology. 2008;181(1):143-55. DOI: 10.1083/jcb.200712058ca
dc.identifier.doi http://dx.doi.org/10.1083/jcb.200712058
dc.identifier.issn 0021-9525
dc.identifier.uri http://hdl.handle.net/10230/25629
dc.language.iso engca
dc.publisher Rockefeller University Pressca
dc.relation.ispartof Journal of cell biology. 2008;181(1):143-55
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/SAF2006-04973
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/SAF2006-13893
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.subject.other Osmosica
dc.subject.other Calcica
dc.title IP3 sensitizes TRPV4 channel to the mechano- and osmotransducing messenger 5'-6'-epoxyeicosatrienoic acidca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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