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Cytokine secretion requires phosphatidylcholine synthesis

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...

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Detalles Bibliográficos
Autores principales: Tian, Yong, Pate, Caroline, Andreolotti, Alberto, Wang, Limin, Tuomanen, Elaine, Boyd, Kelli, Claro, Enrique, Jackowski, Suzanne
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426940/
https://www.ncbi.nlm.nih.gov/pubmed/18559668
http://dx.doi.org/10.1083/jcb.200706152
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author Tian, Yong
Pate, Caroline
Andreolotti, Alberto
Wang, Limin
Tuomanen, Elaine
Boyd, Kelli
Claro, Enrique
Jackowski, Suzanne
author_facet Tian, Yong
Pate, Caroline
Andreolotti, Alberto
Wang, Limin
Tuomanen, Elaine
Boyd, Kelli
Claro, Enrique
Jackowski, Suzanne
author_sort Tian, Yong
collection PubMed
description 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.
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spelling pubmed-24269402008-12-16 Cytokine secretion requires phosphatidylcholine synthesis Tian, Yong Pate, Caroline Andreolotti, Alberto Wang, Limin Tuomanen, Elaine Boyd, Kelli Claro, Enrique Jackowski, Suzanne J Cell Biol Research Articles 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. The Rockefeller University Press 2008-06-16 /pmc/articles/PMC2426940/ /pubmed/18559668 http://dx.doi.org/10.1083/jcb.200706152 Text en © 2008 Tian et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Tian, Yong
Pate, Caroline
Andreolotti, Alberto
Wang, Limin
Tuomanen, Elaine
Boyd, Kelli
Claro, Enrique
Jackowski, Suzanne
Cytokine secretion requires phosphatidylcholine synthesis
title Cytokine secretion requires phosphatidylcholine synthesis
title_full Cytokine secretion requires phosphatidylcholine synthesis
title_fullStr Cytokine secretion requires phosphatidylcholine synthesis
title_full_unstemmed Cytokine secretion requires phosphatidylcholine synthesis
title_short Cytokine secretion requires phosphatidylcholine synthesis
title_sort cytokine secretion requires phosphatidylcholine synthesis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426940/
https://www.ncbi.nlm.nih.gov/pubmed/18559668
http://dx.doi.org/10.1083/jcb.200706152
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