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dc.contributor.authorCasas, Javier
dc.contributor.authorMeana, Clara
dc.contributor.authorLópez-López, José Ramón
dc.contributor.authorBalsinde, Jesús
dc.contributor.authorBalboa, María A.
dc.date.accessioned2024-02-01T15:02:57Z
dc.date.available2024-02-01T15:02:57Z
dc.date.issued2021
dc.identifier.citation1.Casas, J., Meana, C., López-López, J. R., Balsinde, J. & Balboa, M. A. Lipin-1-derived diacylglycerol activates intracellular TRPC3 which is critical for inflammatory signaling. Cell Mol Life Sci 1–18 (2021) doi:10.1007/s00018-021-03999-0.es
dc.identifier.issn1420-682Xes
dc.identifier.urihttps://uvadoc.uva.es/handle/10324/65532
dc.descriptionProducción Científicaes
dc.description.abstractExposure to Gram-negative bacterial LPS exacerbates host immune responses and may lead to sepsis, a life-threatening condition. Despite its high mortality and morbidity, no drugs specifically directed to treating sepsis are currently available. Using human cell genetic depletion, pharmacological inhibition, live-cell microscopy and organelle-targeted molecular sensors we present evidence that the channel TRPC3 is activated intracellularly during macrophage exposure to LPS and is essential for Ca2+ release from internal stores. In this manner, TRPC3 participates in cytosolic Ca2+ elevations, activation of the transcription factor NF-κB and cytokine upregulation. We also report that TRPC3 is activated by diacylglycerol generated by the phosphatidic acid phosphatase lipin-1. In accord with this, lipin-1-deficient cells exhibit reduced Ca2+ responses to LPS challenge. Finally, pharmacological inhibition of TRPC3 reduces systemic inflammation induced by LPS in mice. Collectively, our study unveils a central component of LPS-triggered Ca2+ signaling that involves intracellular sensing of lipin-1-derived DAG by TRPC3, and opens new opportunities for the development of strategies to treat LPS-driven inflammation.es
dc.format.mimetypeapplication/pdfes
dc.language.isoenges
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.titleLipin-1-derived diacylglycerol activates intracellular TRPC3 which is critical for inflammatory signalinges
dc.typeinfo:eu-repo/semantics/articlees
dc.identifier.doi10.1007/s00018-021-03999-0es
dc.identifier.publicationfirstpage8243es
dc.identifier.publicationissue24es
dc.identifier.publicationlastpage8260es
dc.identifier.publicationtitleCellular and Molecular Life Scienceses
dc.identifier.publicationvolume78es
dc.peerreviewedSIes
dc.identifier.essn1420-9071es
dc.rightsCC0 1.0 Universal*
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones


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