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First published online 7 October 2008
doi: 10.1242/jcs.031781

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PI3-kinase signaling contributes to orientation in shallow gradients and enhances speed in steep chemoattractant gradients

Department of Molecular Cell Biology, University of Groningen, Kerklaan 30, 9751NN Haren, The Netherlands

^* Author for correspondence (e-mail: P.J.M.van.Haastert{at}rug.nl)

Accepted 4 August 2008

Dictyostelium cells that chemotax towards cAMP produce phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P₃] at the leading edge, which has been implicated in actin reorganization and pseudopod extension. However, in the absence of PtdIns(3,4,5)P₃ signaling, cells will chemotax via alternative pathways. Here we examined the potential contribution of PtdIns(3,4,5)P₃ to chemotaxis of wild-type cells. The results show that steep cAMP gradients (larger than 10% concentration difference across the cell) induce strong PtdIns(3,4,5)P₃ patches at the leading edge, which has little effect on the orientation but strongly enhances the speed of the cell. Using a new sensitive method for PtdIns(3,4,5)P₃ detection that corrects for the volume of cytosol in pixels at the boundary of the cell, we show that, in shallow cAMP gradient (less than 5% concentration difference across the cell), PtdIns(3,4,5)P₃ is still somewhat enriched at the leading edge. Cells lacking PI3-kinase (PI3K) activity exhibit poor chemotaxis in these shallow gradients. Owing to the reduced speed and diminished orientation of the cells in steep and shallow gradients, respectively, cells lacking PtdIns(3,4,5)P₃ signaling require two- to six-fold longer times to reach a point source of chemoattractant compared with wild-type cells. These results show that, although PI3K signaling is dispensable for chemotaxis, it gives the wild type an advantage over mutant cells.

Key words: Dictyostelium, PI3-kinase, Chemotaxis

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