Phosphoinositide 3-kinase δ regulates membrane fission of Golgi carriers for selective cytokine secretion

Pei Ching Low, Ryo Misaki, Kate Schroder, Amanda C. Stanley, Matthew J. Sweet, Rohan D. Teasdale, Bart Vanhaesebroeck, Frédéric A. Meunier, Tomohiko Taguchi, Jennifer L. Stow

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Abstract

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 p110δ 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 p110δ localizes to the Golgi complex in LPS-activated macrophages, and TNF is loaded into p230-labeled tubules, which cannot undergo fission when p110δ 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 p110δ as part of the membrane fission machinery required at the TGN for the selective trafficking and secretion of cytokines in macrophages.

Original languageEnglish
Pages (from-to)1053-1065
Number of pages13
JournalJournal of Cell Biology
Volume190
Issue number6
DOIs
Publication statusPublished - 2010 Sep 20
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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    Low, P. C., Misaki, R., Schroder, K., Stanley, A. C., Sweet, M. J., Teasdale, R. D., Vanhaesebroeck, B., Meunier, F. A., Taguchi, T., & Stow, J. L. (2010). Phosphoinositide 3-kinase δ regulates membrane fission of Golgi carriers for selective cytokine secretion. Journal of Cell Biology, 190(6), 1053-1065. https://doi.org/10.1083/jcb.201001028