Cytokine secretion requires phosphatidylcholine synthesis.

Tian Y, Pate C, Andreolotti A, Wang L, Tuomanen E, Boyd K, Claro E, Jackowski S
J Cell Biol. 2008 181 (6): 945-57

PMID: 18559668 · PMCID: PMC2426940 · DOI:10.1083/jcb.200706152

Choline cytidylyltransferase (CCT) is the rate-limiting enzyme in the phosphatidylcholine biosynthetic pathway. Here, we demonstrate that CCT alpha-mediated phosphatidylcholine synthesis is required to maintain normal Golgi structure and function as well as cytokine secretion from the Golgi complex. CCT alpha is localized to the trans-Golgi region and its expression is increased in lipopolysaccharide (LPS)-stimulated wild-type macrophages. Although LPS triggers transient reorganization of Golgi morphology in wild-type macrophages, similar structural alterations persist in CCT alpha-deficient cells. Pro-tumor necrosis factor alpha and interleukin-6 remain lodged in the secretory compartment of CCT alpha-deficient macrophages after LPS stimulation. However, the lysosomal-mediated secretion pathways for interleukin-1 beta secretion and constitutive apolipoprotein E secretion are unaltered. Exogenous lysophosphatidylcholine restores LPS-stimulated secretion from CCT alpha-deficient cells, and elevated diacylglycerol levels alone do not impede secretion of pro-tumor necrosis factor alpha or interleukin-6. These results identify CCT alpha as a key component in membrane biogenesis during LPS-stimulated cytokine secretion from the Golgi complex.

MeSH Terms (16)

Animals Bacterial Infections Biomarkers Cytokines Diglycerides Golgi Apparatus Interleukin-6 Lipopolysaccharides Macrophages Mice Models, Biological Nucleotidyltransferases Phosphatidylcholines Protein Processing, Post-Translational Sphingomyelins Tumor Necrosis Factor-alpha

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