Cytokine secretion requires phosphatidylcholine synthesis

Yong Tian, Caroline Pate, Alberto Andreolotti, Limin Wang, Elaine Tuomanen, Kelli Boyd, Enrique Claro, Suzanne Jackowski

Research output: Contribution to journalArticleResearchpeer-review

51 Citations (Scopus)


Choline cytidylyltransferase (CCT) is the rate-limiting enzyme in the phosphatidylcholine biosynthetic pathway. Here, we demonstrate that CCTα-mediated phosphatidylcholine synthesis is required to maintain normal Golgi structure and function as well as cytokine secretion from the Golgi complex. CCTα 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 CCTα-deficient cells. Pro-tumor necrosis factor α and interleukin-6 remain lodged in the secretory compartment of CCTα-deficient macrophages after LPS stimulation. However, the lysosomal-mediated secretion pathways for interleukin-1β secretion and constitutive apolipoprotein E secretion are unaltered. Exogenous lysophosphatidylcholine restores LPS-stimulated secretion from CCTα-deficient cells, and elevated diacylglycerol levels alone do not impede secretion of pro-tumor necrosis factor α or interleukin-6. These results identify CCTα as a key component in membrane biogenesis during LPS-stimulated cytokine secretion from the Golgi complex. © 2008 Tian et al. The Rockefeller University Press.
Original languageEnglish
Pages (from-to)945-957
JournalJournal of Cell Biology
Publication statusPublished - 16 Jun 2008


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