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Published online February 25, 2008
doi:10.1083/jcb.200709180
The Journal of Cell Biology, Vol. 180, No. 4, 747-753
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Veltman et al.
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Four key signaling pathways mediating chemotaxis in Dictyostelium discoideum



Douwe M. Veltman, Ineke Keizer-Gunnik, and Peter J.M. Van Haastert

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

Correspondence to P.J.M. Van Haastert: P.J.M.van.haastert{at}rug.nl

Chemotaxis is the ability of cells to move in the direction of an external gradient of signaling molecules. Cells are guided by actin-filled protrusions in the front, whereas myosin filaments retract the rear of the cell. Previous work demonstrated that chemotaxis of unpolarized amoeboid Dictyostelium discoideum cells is mediated by two parallel pathways, phosphoinositide-3-kinase (PI3K) and phospholipase A2 (PLA2). Here, we show that polarized cells exhibit very good chemotaxis with inhibited PI3K and PLA2 activity. Using genetic screens, we demonstrate that this activity is mediated by a soluble guanylyl cyclase, providing two signals. The protein localizes to the leading edge where it interacts with actin filaments, whereas the cyclic guanosine monophosphate product induces myosin filaments in the rear of the cell. We conclude that chemotaxis is mediated by multiple signaling pathways regulating protrusions at the front and rear of the cell. Cells that express only rear activity are polarized but do not exhibit chemotaxis, whereas cells with only front signaling are unpolarized but undergo chemotaxis.

Abbreviations used in this paper: BPB, bromophenacyl bromide; cGMP, cyclic guanosine monophosphate; IP3, inositol triphosphate; PI3K, phosphoinositide-3-kinase; PIP3, phosphatidylinositol (3,4,5)-trisphosphate; PLA2, phospholipase A2; sGC, soluble guanylyl cyclase.


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