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The EMBO journal
Apr 02, 2001;20 (7): 1620-9.

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

M L Knetsch, N Schäfers, H Horstmann, D J Manstein
Author Information
  1. M L Knetsch: Department of Biophysics, Max-Planck-Institute for Medical Research, D-69120 Heidelberg, Germany.
PMID: 11285226 DOI: 10.1093/emboj/20.7.1620

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.

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MeSH Term

Animals
Dictyostelium
GTPase-Activating Proteins
Guanine Nucleotide Exchange Factors
Protein-Tyrosine Kinases
Proteins
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-bcr
Rho Guanine Nucleotide Exchange Factors
Signal Transduction
rab GTP-Binding Proteins
rac GTP-Binding Proteins

Chemicals

GTPase-Activating Proteins
Guanine Nucleotide Exchange Factors
Proteins
Proto-Oncogene Proteins
Rho Guanine Nucleotide Exchange Factors
rho GTPase-activating protein
Protein-Tyrosine Kinases
Proto-Oncogene Proteins c-bcr
rab GTP-Binding Proteins
rac GTP-Binding Proteins
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

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