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Adv Biol Regul. 2016 Jan;60:36-45. doi: 10.1016/j.jbior.2015.10.005. Epub 2015 Nov 10.

Localizing the lipid products of PI3Kγ in neutrophils.

Author information

1
The Signalling Department, The Babraham Institute, The Babraham Research Campus, Cambridge, CB22 3AT, United Kingdom.
2
Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK; Division of Cell Biology and Immunology, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
3
Laboratoire de Pharmacologie et Toxicologie, INRA UR66, Toulouse, France.
4
Division of Cell Biology and Immunology, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
5
The Imaging Facility, The Babraham Institute, The Babraham Research Campus, Cambridge, CB22 3AT, UK.
6
The Bioinformatics Group, The Babraham Institute, The Babraham Research Campus, Cambridge, CB22 3AT, UK.
7
UCB, Allée de la Recherche, 60 1070 Brussels, Belgium.
8
Developmental and Molecular Pathways, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, USA.
9
Department of Pathology and Immunology, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
10
Warwick Systems Biology Centre, University of Warwick, UK.
11
The Signalling Department, The Babraham Institute, The Babraham Research Campus, Cambridge, CB22 3AT, United Kingdom. Electronic address: len.stephens@bbsrc.ac.uk.

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 reportersand 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.

KEYWORDS:

Neutrophil; PI3K; Polarization

PMID:
26596865
PMCID:
PMC4739120
DOI:
10.1016/j.jbior.2015.10.005
[Indexed for MEDLINE]
Free PMC Article

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