RRC ID 6650
Author Wilkins A, Chubb JR, Insall RH.
Title A novel Dictyostelium RasGEF is required for normal endocytosis, cell motility and multicellular development.
Journal Curr Biol
Abstract BACKGROUND:Dictyostelium possesses a surprisingly large number of Ras proteins and little is known about their activators, the guanine nucleotide exchange factors (GEFs). It is also unclear, in Dictyostelium or in higher eukaryotes, whether Ras pathways are linear, with each Ras controlled by its own GEF, or networked, with multiple GEFs acting on multiple Ras proteins.
RESULTS:We have identified the Dictyostelium gene that encodes RasGEFB, a protein with homology to known RasGEFs such as the Son-of-sevenless (Sos) protein. Dictyostelium cells in which the gene for RasGEFB was disrupted moved unusually rapidly, but lost the ability to perform macropinocytosis and therefore to grow in liquid medium. Crowns, the sites of macropinocytosis, were replaced by polarised lamellipodia. Mutant cells were also profoundly defective in early development, although they eventually formed tiny but normally proportioned fruiting bodies. This defect correlated with loss of discoidin Igamma mRNA, a starvation-induced gene, although other genes required for development were expressed normally or even precociously. RasGEFB was able to rescue a Saccharomyces CDC25 mutant, indicating that it is a genuine GEF for Ras proteins.
CONCLUSIONS:RasGEFB appears to be the principal activator of the RasS protein, which regulates macropinocytosis and cell speed, but it also appears to regulate one or more other Ras proteins.
Volume 10(22)
Pages 1427-37
Published 2000-11-16
DOI 10.1016/s0960-9822(00)00797-1
PII S0960-9822(00)00797-1
PMID 11102804
MeSH Amino Acid Sequence Animals Base Sequence Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Cell Movement Cloning, Molecular DNA, Complementary Dictyostelium / genetics Dictyostelium / growth & development Dictyostelium / metabolism Dictyostelium / physiology Endocytosis / physiology* Fungal Proteins / genetics Fungal Proteins / metabolism Gene Expression Gene Targeting Molecular Sequence Data Mutagenesis Phagocytosis / physiology Saccharomyces cerevisiae ras Guanine Nucleotide Exchange Factors / genetics ras Guanine Nucleotide Exchange Factors / metabolism* ras Guanine Nucleotide Exchange Factors / physiology ras-GRF1 / genetics ras-GRF1 / metabolism
IF 9.601
Times Cited 24
Cellular slime molds G24893 S90283