title: The Dictyostelium genome encodes numerous RasGEFs with multiple biological roles.
abstract: BACKGROUND
  Dictyostelium discoideum is a eukaryote with a simple lifestyle and a relatively small genome whose sequence has been fully determined. It is widely used for studies on cell signaling, movement and multicellular development. Ras guanine-nucleotide exchange factors (RasGEFs) are the proteins that activate Ras and thus lie near the top of many signaling pathways. They are particularly important for signaling in development and chemotaxis in many organisms, including Dictyostelium.
  
  
  RESULTS
  We have searched the genome for sequences encoding RasGEFs. Despite its relative simplicity, we find that the Dictyostelium genome encodes at least 25 RasGEFs, with a few other genes encoding only parts of the RasGEF consensus domains. All appear to be expressed at some point in development. The 25 genes include a wide variety of domain structures, most of which have not been seen in other organisms. The LisH domain, which is associated with microtubule binding, is seen particularly frequently; other domains that confer interactions with the cytoskeleton are also common. Disruption of a sample of the novel genes reveals that many have clear phenotypes, including altered morphology and defects in chemotaxis, slug phototaxis and thermotaxis.
  
  
  CONCLUSIONS
  These results suggest that the unexpectedly large number of RasGEF genes reflects an evolutionary expansion of the range of Ras signaling rather than functional redundancy or the presence of multiple pseudogenes.
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK. awilkins@caregroup.harvard.edu
authors.forename: Andrew
authors.initials: A
authors.lastname: Wilkins
authors.forename: Karol
authors.initials: K
authors.lastname: Szafranski
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Fraser
authors.forename: Deenadayalan
authors.initials: D
authors.lastname: Bakthavatsalam
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
authors.forename: Paul R
authors.initials: PR
authors.lastname: Fisher
authors.forename: Gernot
authors.initials: G
authors.lastname: Glöckner
authors.forename: Ludwig
authors.initials: L
authors.lastname: Eichinger
authors.forename: Angelika A
authors.initials: AA
authors.lastname: Noegel
authors.forename: Robert H
authors.initials: RH
authors.lastname: Insall
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D004023:Dictyostelium / Q000166:cytology / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D017125:Genes, Protozoan / Q000235:genetics*; D018503:Genome, Protozoan / Q000235:genetics*; D005856:Germ-Free Life; D009068:Movement; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA; D020663:ras Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D020663:ras Guanine Nucleotide Exchange Factors; D020741:rho GTP-Binding Proteins