Lipin-1-derived diacylglycerol activates intracellular TRPC3 which is critical for inflammatory signaling.

ABSTRACT: Exposure 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 lipi

SUBMITTER: Casas J 

PROVIDER: S-EPMC8629864 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature