PIP3-dependent macropinocytosis is incompatible with chemotaxis

Veltman, D.M., Lemieux, M.G., Knecht, D.A. and Insall, R.H. (2014) PIP3-dependent macropinocytosis is incompatible with chemotaxis. Journal of Cell Biology, 204(4), pp. 497-505. (doi: 10.1083/jcb.201309081)

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In eukaryotic chemotaxis, the mechanisms connecting external signals to the motile apparatus remain unclear. The role of the lipid phosphatidylinositol 3,4,5-trisphosphate (PIP3) has been particularly controversial. PIP3 has many cellular roles, notably in growth control and macropinocytosis as well as cell motility. Here we show that PIP3 is not only unnecessary for Dictyostelium discoideum to migrate toward folate, but actively inhibits chemotaxis. We find that macropinosomes, but not pseudopods, in growing cells are dependent on PIP3. PIP3 patches in these cells show no directional bias, and overall only PIP3-free pseudopods orient up-gradient. The pseudopod driver suppressor of cAR mutations (SCAR)/WASP and verprolin homologue (WAVE) is not recruited to the center of PIP3 patches, just the edges, where it causes macropinosome formation. Wild-type cells, unlike the widely used axenic mutants, show little macropinocytosis and few large PIP3 patches, but migrate more efficiently toward folate. Tellingly, folate chemotaxis in axenic cells is rescued by knocking out phosphatidylinositide 3-kinases (PI 3-kinases). Thus PIP3 promotes macropinocytosis and interferes with pseudopod orientation during chemotaxis of growing cells.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Insall, Professor Robert
Authors: Veltman, D.M., Lemieux, M.G., Knecht, D.A., and Insall, R.H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Journal of Cell Biology
Publisher:Rockefeller University Press
ISSN (Online):1540-8140
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in the Journal of Cell Biology 204(4):497-505
Publisher Policy:Reproduced under a Creative Commons License

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