The Dictyostelium genome encodes numerous RasGEFs with multiple biological roles.
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.
Wilkins
Andrew
A
School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK. awilkins@caregroup.harvard.edu
Szafranski
Karol
K
Fraser
Derek J
DJ
Bakthavatsalam
Deenadayalan
D
Müller
Rolf
R
Fisher
Paul R
PR
Glöckner
Gernot
G
Eichinger
Ludwig
L
Noegel
Angelika A
AA
Insall
Robert H
RH
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
D000199:Actins; D020663:ras Guanine Nucleotide Exchange Factors; D020741:rho GTP-Binding Proteins