Localizing the lipid products of PI3Kγ in neutrophils

Laura Norton, Yvonne Lindsay, Arnaud Deladeriere, Tamara Chessa, Hervé Guillou, Sabine Suire, John Lucocq, Simon Walker, Simon Andrews, Anne Segonds-Pichon, Oliver Rausch, Peter Finan, Takehiko Sasaki, Cheng-Jin Du, Till Bretschneider, G John Ferguson, Phillip T Hawkins, Len Stephens

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Class I phosphoinositide 3-kinases (PI3Ks) are important regulators of neutrophil migration in response to a range of chemoattractants. Their primary lipid products PtdIns(3,4,5)P3 and PtdIns(3,4)P2 preferentially accumulate near to the leading edge of migrating cells and are thought to act as an important cue organizing molecular and morphological polarization. We have investigated the distribution and accumulation of these lipids independently in mouse neutrophils using eGFP-PH reporters and electron microscopy (EM). We found that authentic mouse neutrophils rapidly polarized their Class I PI3K signalling, as read-out by eGFP-PH reporters, both at the up-gradient leading edge in response to local stimulation with fMLP as well as spontaneously and randomly in response to uniform stimulation. EM studies revealed these events occurred at the plasma membrane, were dominated by accumulation of PtdIns(3,4,5)P3, but not PtdIns(3,4)P2, and were dependent on PI3Kγ and its upstream activation by both Ras and Gβγs.
Original languageEnglish
Pages (from-to)36-45
JournalAdvances in Biological Regulation
Volume60
Early online date10 Nov 2015
DOIs
Publication statusPublished - Jan 2016

Keywords

  • PI3K
  • Neutrophil
  • Polarization

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