A novel Dictyostelium RasGEF is required for normal endocytosis, cell motility and multicellular development

Wilkins, A., Chubb, J. R. and Insall, R. H. (2000) A novel Dictyostelium RasGEF is required for normal endocytosis, cell motility and multicellular development. Current Biology, 10(22), pp. 1427-1437. (doi:10.1016/S0960-9822(00)00797-1) (PMID:11102804)

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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 Iγ 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Insall, Professor Robert
Authors: Wilkins, A., Chubb, J. R., and Insall, R. H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Current Biology
Publisher:Elsevier
ISSN:0960-9822
ISSN (Online):1879-0445
Published Online:27 November 2000

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