Letter abstract
Nature Cell Biology 9, 86 - 91 (2006)
Published online: 17 December 2006 | doi:10.1038/ncb1517
PI(3)K
has an important context-dependent role in neutrophil chemokinesis
G. John Ferguson1, Laura Milne1, Suhasini Kulkarni1, Takehiko Sasaki2, Simon Walker1, Simon Andrews1, Tom Crabbe3, Peter Finan4, Gareth Jones5, Shaun Jackson6, Montserrat Camps7, Christian Rommel7, Matthias Wymann8, Emilio Hirsch9, Phillip Hawkins1,10 & Len Stephens1,10
The directional movement of cells in a gradient of external stimulus is termed chemotaxis and is important in many aspects of development and differentiated cell function. Phophoinositide 3-kinases (PI(3)Ks) are thought to have critical roles within the gradient-sensing machinery of a variety of highly motile cells1, 2, such as mammalian phagocytes3, allowing these cells to respond quickly and efficiently to shallow gradients of soluble stimuli. Our analysis of mammalian neutrophil migration towards ligands such as fMLP shows that, although PtdIns(3,4)P2 and PtdIns(3,4,5)P3 accumulate in a PI(3)K
-dependent fashion at the up-gradient leading-edge, this signal is not required for efficient gradient-sensing and gradient-biased movement. PI(3)K activity is however, a critical determinant of the proportion of cells that can move, that is, respond chemokinetically, in reaction to fMLP. Furthermore, this dependence of chemokinesis on PI(3)K activity is context dependent, both with respect to the state of priming of the neutrophils and the type of surface on which they are migrating. We propose this effect of PI(3)K is through roles in the regulation of some aspects of neutrophil polarization that are relevant to movement, such as integrin-based adhesion and the accumulation of polymerized (F)-actin at the leading-edge.
- The Babraham Institute, Cambridge, CB22 3AT, UK.
- Akita University, Akita, Japan.
- UCB, Slough, Berkshire, SL1 4EN, UK.
- Novartis, Cambridge, USA.
- Kings College London, SE1 1UL, UK.
- Monash University, Melbourne, Victoria 3004, Australia.
- Serono Research Institute, Geneva, CH-1211, Switzerland.
- DKBW University, Basel, CH-4508, Switzerland.
- University of Torino, 10126, Torino, Italy.
- These authors contributed equally to this work.
Correspondence to: Len Stephens1,10 e-mail: len.stephens@bbsrc.ac.uk
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