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

doi:10.1016/j.jbior.2015.10.005

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 journal › Article › peer-review

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 language	English
Pages (from-to)	36-45
Journal	Advances in Biological Regulation
Volume	60
Early online date	10 Nov 2015
DOIs	https://doi.org/10.1016/j.jbior.2015.10.005
Publication status	Published - Jan 2016

Keywords

PI3K
Neutrophil
Polarization

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10.1016/j.jbior.2015.10.005Licence: CC BY

Norton_2016_ADVBIOLREG_CC-BY
© 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/ 4.0/).
Final published version, 1.83 MBLicence: CC BY

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Norton, L., Lindsay, Y., Deladeriere, A., Chessa, T., Guillou, H., Suire, S., Lucocq, J., Walker, S., Andrews, S., Segonds-Pichon, A., Rausch, O., Finan, P., Sasaki, T., Du, C.-J., Bretschneider, T., Ferguson, G. J., Hawkins, P. T., & Stephens, L. (2016). Localizing the lipid products of PI3Kγ in neutrophils. Advances in Biological Regulation, 60, 36-45. https://doi.org/10.1016/j.jbior.2015.10.005

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title = "Localizing the lipid products of PI3Kγ in neutrophils",

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.",

keywords = "PI3K, Neutrophil, Polarization",

author = "Laura Norton and Yvonne Lindsay and Arnaud Deladeriere and Tamara Chessa and Herv{\'e} Guillou and Sabine Suire and John Lucocq and Simon Walker and Simon Andrews and Anne Segonds-Pichon and Oliver Rausch and Peter Finan and Takehiko Sasaki and Cheng-Jin Du and Till Bretschneider and Ferguson, {G John} and Hawkins, {Phillip T} and Len Stephens",

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Norton, L, Lindsay, Y, Deladeriere, A, Chessa, T, Guillou, H, Suire, S, Lucocq, J, Walker, S, Andrews, S, Segonds-Pichon, A, Rausch, O, Finan, P, Sasaki, T, Du, C-J, Bretschneider, T, Ferguson, GJ, Hawkins, PT & Stephens, L 2016, 'Localizing the lipid products of PI3Kγ in neutrophils', Advances in Biological Regulation, vol. 60, pp. 36-45. https://doi.org/10.1016/j.jbior.2015.10.005

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T1 - Localizing the lipid products of PI3Kγ in neutrophils

AU - Norton, Laura

AU - Lindsay, Yvonne

AU - Deladeriere, Arnaud

AU - Chessa, Tamara

AU - Guillou, Hervé

AU - Suire, Sabine

AU - Lucocq, John

AU - Walker, Simon

AU - Andrews, Simon

AU - Segonds-Pichon, Anne

AU - Rausch, Oliver

AU - Finan, Peter

AU - Sasaki, Takehiko

AU - Du, Cheng-Jin

AU - Bretschneider, Till

AU - Ferguson, G John

AU - Hawkins, Phillip T

AU - Stephens, Len

PY - 2016/1

Y1 - 2016/1

N2 - 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.

AB - 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.

KW - PI3K

KW - Neutrophil

KW - Polarization

U2 - 10.1016/j.jbior.2015.10.005

DO - 10.1016/j.jbior.2015.10.005

M3 - Article

C2 - 26596865

SN - 2212-4934

VL - 60

SP - 36

EP - 45

JO - Advances in Biological Regulation

JF - Advances in Biological Regulation

ER -

Localizing the lipid products of PI3Kγ in neutrophils

Abstract

Keywords

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