Your browser version may not work well with NCBI's Web applications. More information here...
1: J Cell Biol. 2008 Jun 16;181(6):945-57.
Related Articles, Links
Click here to read Click here to read
Cytokine secretion requires phosphatidylcholine synthesis.

Tian Y, Pate C, Andreolotti A, Wang L, Tuomanen E, Boyd K, Claro E, Jackowski S.

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

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.

Publication Types:
PMID: 18559668 [PubMed - indexed for MEDLINE]

PMCID: PMC2426940 [Available on 12/16/08]