dictyNews Electronic Edition Volume 29, number 9 September 28, 2007 Please submit abstracts of your papers as soon as they have been accepted for publication by sending them to dicty@northwestern.edu or by using the form at http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit. Back issues of dictyNews, the Dicty Reference database and other useful information is available at dictyBase - http://dictybase.org. ========= Abstracts ========= Chemotaxis: Navigating by Multiple Signaling Pathways Peter J. M. Van Haastert and Douwe M. Veltman Science’s STKE, pe40 During chemotaxis, phosphatidylinositol 3,4,5-trisphosphate (PIP3) accumulates at the leading edge of a eukaryotic cell, where it induces the formation of pseudopodia. PIP3 has been suggested to be the compass of cells navigating in gradients of signaling molecules. Recent observations suggest that chemotaxis is more complex than previously anticipated. Complete inhibition of all PIP3 signaling has little effect, and alternative pathways have been identified. In addition, selective pseudopod growth and retraction are more important in directing cell movement than is the place where new pseudopodia are formed. Submitted by: Peter Van Haastert [p.j.m.van.haastert@rug.nl] -------------------------------------------------------------------------------- PLC regulation of PI(3,4,5)P3-mediated chemotaxis Arjan Kortholt*, Jason King*, Ineke Keizer-Gunnink, Adrian Harwood and Peter J.M. Van Haastert * these authors contributed equally to this work Department of Molecular Cell Biology, University of Groningen, Kerklaan 30, 9751NN Haren, the Netherlands School of Biosciences, Cardiff University, Museum Avenue, Cardiff, UK. CF10 3US Molecular Biology of the Cell, in press Generation of a PI(3,4,5)P3 gradient within the plasma membrane is important for cell polarization and chemotaxis in many eukaryotic cells. The gradient is produced by the combined activity of PI3K to increase PI(3,4,5)P3 on the membrane nearest the polarizing signal and PI(3,4,5)P3 dephosphorylation by PTEN elsewhere. Common to both of these enzymes is the lipid PI(4,5)P2, which is not only the substrate of PI3K and product of PTEN, but is also important for membrane binding of PTEN. Consequently, regulation of PLC activity, which hydrolyses PI(4,5)P2, could have important consequences for PI(3,4,5)P3 localization. We investigate the role of PLC in PI(3,4,5)P3 mediated chemotaxis in Dictyostelium. plc-null cells are resistant to the PI3K inhibitor LY294002 and produce little PI(3,4,5)P3 after cAMP stimulation, as monitored by the PI(3,4,5)P3-specific PH-domain of CRAC (PHCRACGFP). In contrast, PLC overexpression elevates PI(3,4,5)P3 and impairs chemotaxis in a similar way to loss of pten. PI3K localisation at the leading edge of plc-null cells is unaltered, but dissociation of PTEN from the membrane is strongly reduced in both gradient and uniform stimulation with cAMP. These results indicate that local activation of PLC can control PTEN localization and suggest a novel mechanism to regulate the internal PI(3,4,5)P3 gradient. Submitted by: Peter Van Haastert [p.j.m.van.haastert@rug.nl] ============================================================== [End dictyNews, volume 29, number 9]