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The Dictyostelium Bcr/Abr-related protein DRG regulates both Rac- and Rab-dependent pathways

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Horstmann,  Heinz
Department of Biomedical Optics, Max Planck Institute for Medical Research, Max Planck Society;
Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society;

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Manstein,  Dietmar J.
Emeritus Group Biophysics, Max Planck Institute for Medical Research, Max Planck Society;

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Citation

Knetsch, M. L. W., Schäfers, N., Horstmann, H., & Manstein, D. J. (2001). The Dictyostelium Bcr/Abr-related protein DRG regulates both Rac- and Rab-dependent pathways. EMBO Journal, 20(7), 1620-1629. doi:10.1093/emboj/20.7.1620.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0028-F0E6-3
Abstract
Dictyostelium discoideum DdRacGap1 (DRG) contains both Rho-GEF and Rho-GAP domains, a feature it shares with mammalian Bcr and Abr. To elucidate the physiological role of this multifunctional protein, we characterized the enzymatic activity of recombinant DRG fragments in vitro, created DRG-null cells, and studied the function of the protein in vivo by analysing the phenotypic changes displayed by DRG-depleted cells and DRG-null cells complemented with DRG or DRG fragments. Our results show that DRG-GEF modulates F-actin dynamics and cAMP-induced F-actin formation via Rac1-dependent signalling pathways. DRG's RacE-GAP activity is required for proper cytokinesis to occur. Additionally, we provide evidence that the specificity of DRG is not limited to members of the Rho family of small GTPases. A recombinant DRG-GAP accelerates the GTP hydrolysis of RabD 30-fold in vitro and our complementation studies show that DRG-GAP activity is required for the RabD-dependent regulation of the contractile vacuole system in Dictyostelium.