Research ArticleGPCR SIGNALING

Phosphatidylinositol 4-phosphate is a major source of GPCR-stimulated phosphoinositide production

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Sci. Signal.  11 Sep 2018:
Vol. 11, Issue 547, eaan1210
DOI: 10.1126/scisignal.aan1210

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Sourcing phosphoinositides

Agonist binding to certain G protein–coupled receptors (GPCRs) stimulates members of the phospholipase C (PLC) family of enzymes to hydrolyze the plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (PI4,5P2), which results in the generation of the intracellular second messengers DAG and IP3. Noting that certain PLCs also hydrolyze the lipid phosphatidylinositol 4-phosphate (PI4P) at the Golgi, de Rubio et al. performed fluorescence-based imaging to monitor the spatiotemporal regulation of lipid hydrolysis in various cell types stimulated through different GPCRs, as well as the resulting activation of the DAG-dependent kinase PKD. Their findings suggest that PI4P, but not PI4,5P2, at the plasma membrane is the main source of GPCR-stimulated second messenger production.