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Article

  • The EMBO Journal (2004) 23, 4177 - 4189
  • doi:10.1038/sj.emboj.7600368

Published online: 7 October 2004

Rac regulation of chemotaxis and morphogenesis in Dictyostelium

Kyung Chan Park1, Francisco Rivero2, Ruedi Meili1, Susan Lee1, Fabio Apone1,a and Richard A Firtel1

  1. Section of Cell and Developmental Biology, Division of Biological Sciences, Center for Molecular Genetics, University of California, San Diego, La Jolla, CA, USA
  2. Zentrum für Biochemie der Medizinischen Fakultät, Universität zu Köln, Köln, Germany

Correspondence to:

Richard A Firtel, University of California, Natural Sciences Building, Room 6316, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0380, USA. Tel.: +1 858 534 2788; Fax: +1 858 822 5900; E-mail: rafirtel@ucsd.edu

aPresent address: Arterra Bioscience srl, via Comunale Margherita, 482, 80145 Naples, Italy

Received 17 March 2004; Accepted 27 July 2004

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.

  • Keywords:

    • chemotaxis,
    • Dictyostelium,
    • morphogenesis,
    • Rac,
    • PI3K