Rac regulation of chemotaxis and morphogenesis in Dictyostelium

• Published in: The EMBO journal Vol. 23; no. 21; pp. 4177 - 4189
• Main Authors: Park, Kyung Chan, Rivero, Francisco, Meili, Ruedi, Lee, Susan, Apone, Fabio, Firtel, Richard A
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 27.10.2004; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: Actins - metabolism; Amino Acid Sequence; Animals; Cell Shape; Chemotactic Factors - metabolism; chemotaxis; Chemotaxis - physiology; Dictyostelium; Dictyostelium - cytology; Dictyostelium - physiology; Enzyme Activation; Kinetics; Molecular Sequence Data; Morphogenesis; Myosin Type II - metabolism; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; PI3K; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Rac; rac GTP-Binding Proteins - genetics; rac GTP-Binding Proteins - metabolism; Signal Transduction - physiology
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/sj.emboj.7600368

Chemotaxis requires localized F‐actin polymerization at the site of the plasma membrane closest to the chemoattractant source, a process controlled by Rac/Cdc42 GTPases. We identify Dictyostelium RacB as an essential mediator of this process. RacB is activated upon chemoattractant stimulation, exhibiting biphasic kinetics paralleling F‐actin polymerization. racB null cells have strong chemotaxis and morphogenesis defects and a severely reduced chemoattractant‐mediated F‐actin polymerization and PAKc activation. RacB activation is partly controlled by the PI3K pathway. pi3k1/2 null cells and wild‐type cells treated with LY294002 exhibit a significantly reduced second peak of RacB activation, which is linked to pseudopod extension, whereas a PTEN hypomorph exhibits elevated RacB activation. We identify a RacGEF, RacGEF1, which has specificity for RacB in vitro. racgef1 null cells exhibit reduced RacB activation and cells expressing mutant RacGEF1 proteins display chemotaxis and morphogenesis defects. RacGEF1 localizes to sites of F‐actin polymerization. Inhibition of this localization reduces RacB activation, suggesting a feedback loop from RacB via F‐actin polymerization to RacGEF1. Our findings provide a critical linkage between chemoattractant stimulation, F‐actin polymerization, and chemotaxis in Dictyostelium.