Phosphoinositide 3-kinase [delta] regulates membrane fission of Golgi carriers for selective cytokine secretion

Phosphoinositide 3-kinase (PI3K) p110 isoforms are membrane lipid kinases classically involved in signal transduction. Lipopolysaccharide (LPS)-activated macrophages constitutively and abundantly secrete proinflammatory cytokines including tumor necrosis factor-α (TNF). Loss of function of the p110....

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Bibliographic Details
Published inThe Journal of cell biology Vol. 190; no. 6; p. 1053
Main Authors Low, Pei Ching, Misaki, Ryo, Schroder, Kate, Stanley, Amanda C, Sweet, Matthew J, Teasdale, Rohan D, Vanhaesebroeck, Bart, Meunier, Frédéric A, Taguchi, Tomohiko, Stow, Jennifer L
Format Journal Article
LanguageEnglish
Published New York Rockefeller University Press 20.09.2010
Subjects
Cells
Cytokines
Histology
Kinases
Lipids
Membranes
Rodents
Signal transduction
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Summary:Phosphoinositide 3-kinase (PI3K) p110 isoforms are membrane lipid kinases classically involved in signal transduction. Lipopolysaccharide (LPS)-activated macrophages constitutively and abundantly secrete proinflammatory cytokines including tumor necrosis factor-α (TNF). Loss of function of the p110... isoform of PI3K using inhibitors, RNA-mediated knockdown, or genetic inactivation in mice abolishes TNF trafficking and secretion, trapping TNF in tubular carriers at the trans-Golgi network (TGN). Kinase-active p110... localizes to the Golgi complex in LPS-activated macrophages, and TNF is loaded into p230-labeled tubules, which cannot undergo fission when p110... is inactivated. Similar blocks in fission of these tubules and in TNF secretion result from inhibition of the guanosine triphosphatase dynamin 2. These findings demonstrate a new function for p110... as part of the membrane fission machinery required at the TGN for the selective trafficking and secretion of cytokines in macrophages. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:0021-9525
1540-8140