Phospholipase D promotes lipid microdomain-associated signaling events in mast cells

Felipe A. Lisboa, Ze Peng, Christian A. Combs, Michael A. Beaven

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Initial IgE-dependent signaling events are associated with detergent-resistant membrane microdomains. Following Ag stimulation, the IgE-receptor (FcεRI) accumulates within these domains. This facilitates the phosphorylation of FcεRI subunits by the Src kinase, Lyn, and the interaction with adaptor proteins, such as the linker for activation of T cells. Among the phospholipases (PL) subsequently activated, PLD is of interest because of its presence in lipid microdomains and the possibility that its product, phosphatidic acid, may regulate signal transduction and membrane trafficking. We find that in Ag-stimulated RBL-2H3 mast cells, the association of FcεRI with detergent-resistant membrane fractions is inhibited by 1-butanol, which subverts production of phosphatidic acid to the biologically inert phosphatidylbutanol. Furthermore, the knockdown of PLD2, and to a lesser extent PLD1 with small inhibitory RNAs, also suppressed the accumulation of FcεRI and Lyn in these fractions as well as the phosphorylation of Src kinases, FcεRI, linker for activation of T cells, and degranulation. These effects were accompanied by changes in distribution of the lipid microdomain component, ganglioside 1, in the plasma membrane as determined by binding of fluorescent-tagged cholera toxin B subunit and confocal microscopy in live cells. Collectively, these findings suggest that PLD activity plays an important role in promoting IgE-dependent signaling events within lipid microdomains in mast cells.

Original languageEnglish
Pages (from-to)5104-5112
Number of pages9
JournalJournal of Immunology
Issue number8
StatePublished - 15 Oct 2009
Externally publishedYes


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