Cytokine secretion requires phosphatidylcholine synthesis
Tian, Yong (St. Jude Children's Research Hospital (Memphis, Estats Units d'Amèrica))
Pate, Caroline (St. Jude Children's Research Hospital (Memphis, Estats Units d'Amèrica))
Garcia Andreolotti, Alberto (Universitat Autònoma de Barcelona. Institut de Neurociències)
Wang, Limin (St. Jude Children's Research Hospital (Memphis, Estats Units d'Amèrica))
Tuomanen, Elaine (St. Jude Children's Research Hospital (Memphis, Estats Units d'Amèrica))
Boyd, Kelli (St. Jude Children's Research Hospital (Memphis, Estats Units d'Amèrica))
Claro Izaguirre, Enrique (Universitat Autònoma de Barcelona. Institut de Neurociències)
Jackowski, Suzanne (St. Jude Children's Research Hospital (Memphis, Estats Units d'Amèrica))

Date:	2008
Abstract:	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.
Grants:	Ministerio de Educación y Ciencia SAF2004-1698
Note:	Altres ajuts: Cancer Center (CORE) Support grant CA 21765, i l'American Lebanese Syrian Associated Charities
Note:	Altres ajuts: NIH/GM45737
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials i que es distribueixin sota la mateixa llicència que regula l'obra original. Cal que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	The Journal of cell biology, Vol. 181, Num. 6 (June 2008) , p. 945-957, ISSN 0021-9525

DOI: 10.1083/jcb.200706152
PMID: 18559668

13 p, 4.1 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles