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PMID: 11285226 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 20 ·No. 7 ·2001-04-02 ·Pages 1620-9

Knetsch ML, Schäfers N, Horstmann H, Manstein DJ

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.

MeSH Terms
Animals Dictyostelium GTPase-Activating Proteins/genetics,metabolism,physiology Guanine Nucleotide Exchange Factors/genetics,metabolism,physiology Protein-Tyrosine Kinases Proteins/genetics,metabolism,physiology Proto-Oncogene Proteins/genetics,metabolism,physiology Proto-Oncogene Proteins c-bcr Rho Guanine Nucleotide Exchange Factors Signal Transduction rab GTP-Binding Proteins/metabolism rac GTP-Binding Proteins/metabolism
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
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Knetsch M L
Department of Biophysics, Max-Planck-Institute for Medical Research, D-69120 Heidelberg, Germany.
Schäfers N
Horstmann H
Manstein D J
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.7.1620
Published
2001-04-02
Pages
1620-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC145496
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/20.7.1620 PMC Full Text View journal details
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