Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1782156307447414784 |
---|---|
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. |
format | Text |
id | pubmed-2426940 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT tianyong cytokinesecretionrequiresphosphatidylcholinesynthesis AT patecaroline cytokinesecretionrequiresphosphatidylcholinesynthesis AT andreolottialberto cytokinesecretionrequiresphosphatidylcholinesynthesis AT wanglimin cytokinesecretionrequiresphosphatidylcholinesynthesis AT tuomanenelaine cytokinesecretionrequiresphosphatidylcholinesynthesis AT boydkelli cytokinesecretionrequiresphosphatidylcholinesynthesis AT claroenrique cytokinesecretionrequiresphosphatidylcholinesynthesis AT jackowskisuzanne cytokinesecretionrequiresphosphatidylcholinesynthesis |