Rho GTPase signaling in Dictyostelium discoideum: Insights from the genome

Vlahou, Georgia; Rivero, Francisco

doi:10.1016/j.ejcb.2006.04.011

Cited by 70 publications

(80 citation statements)

References 70 publications

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“…These genes encode proteins with N-terminal FCH and predicted coiled-coil domains and a C-terminal SH3 domain but no RhoGAP domains. Their domain organisations are similar to Syndapin (Qualmann et al, 1999) and Nwk/Bzz1p (Soulard et al, 2002;Coyle et al, 2004;Vlahou and Rivero, 2006), respectively (Fig. 1A).…”

Section: Resultsmentioning

confidence: 92%

Dictyostelium MEGAPs: F-BAR domain proteins that regulate motility and membrane tubulation in contractile vacuoles

Heath

Insall

2008

Journal of Cell Science

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PCH family proteins are fundamentally important proteins, linking membrane curvature events with cytoskeletal reorganisation. One group, the MEGAPs (also called srGAPs and WRPs) contain RhoGAP domains in addition to the F-BAR domain. We disrupted MEGAP1 and MEGAP2 in Dictyostelium both singly and in combination. We found a strong cytoskeletal phenotype in MEGAP1– cells and a subtle phototaxis defect in MEGAP2– slugs. MEGAP1–/2– cells have an overabundance of filopodia and slug motility and function are affected. The most dramatic changes, however, are on contractile vacuoles. MEGAP1–/2– cells empty their contractile vacuoles less efficiently than normal and consequently have three times the usual number. GFP-tagged MEGAP1 localises to tubules of the contractile vacuole network and when vacuoles start to empty they recruit cytosolic GFP-MEGAP1. Mutants in the Saccharomyces homologues RGD1 and RGD2 also show abnormal vacuoles, implying that this role is conserved. Thus, MEGAP is an important regulator of the contractile vacuole network, and we propose that tubulation of the contractile vacuole by MEGAP1 represents a novel mechanism for driving vacuole emptying.

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Section: Resultsmentioning

confidence: 92%

Dictyostelium MEGAPs: F-BAR domain proteins that regulate motility and membrane tubulation in contractile vacuoles

Heath

Insall

2008

Journal of Cell Science

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“…Dock180 interacts with mammalian Rac1 through the CZH2 domain and mediates its activation (Kiyokawa et al, 1998;Nolan et al, 1998;Fukui et al, 2001;Meller et al, 2005;Watabe-Uchida et al, 2006). In Dictyostelium, a few members of the Rho family can be loosely grouped into the Rac subfamily, and Rac1A/B/C are the closest homologues to the mammalian Rac (they show Ͼ85% identity to human Rac1; Rivero et al, 2001;Rivero and Somesh, 2002;Vlahou and Rivero, 2006). As previously reported in other systems, Dictyostelium Racs regulate the basal levels of F-actin assembly, therefore playing a crucial role in an array of cellular activities that depend on the remodeling of the actin cytoskeleton (Ridley, 2006;Ladwein and Rottner, 2008).…”

Section: Dockd Forms a Complex With Dictyostelium Elmo1 And Rac Gtpasesmentioning

confidence: 99%

DictyosteliumDock180-related RacGEFs Regulate the Actin Cytoskeleton during Cell Motility

Para

Krischke

Merlot

et al. 2009

MBoC

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Cell motility of amoeboid cells is mediated by localized F-actin polymerization that drives the extension of membrane protrusions to promote forward movements. We show that deletion of either of two members of the Dictyostelium Dock180 family of RacGEFs, DockA and DockD, causes decreased speed of chemotaxing cells. The phenotype is enhanced in the double mutant and expression of DockA or DockD complements the reduced speed of randomly moving DockD null cells' phenotype, suggesting that DockA and DockD are likely to act redundantly and to have similar functions in regulating cell movement. In this regard, we find that overexpressing DockD causes increased cell speed by enhancing F-actin polymerization at the sites of pseudopod extension. DockD localizes to the cell cortex upon chemoattractant stimulation and at the leading edge of migrating cells and this localization is dependent on PI3K activity, suggesting that DockD might be part of the pathway that links PtdIns(3,4,5)P 3 production to F-actin polymerization. Using a proteomic approach, we found that DdELMO1 is associated with DockD and that Rac1A and RacC are possible in vivo DockD substrates. In conclusion, our work provides a further understanding of how cell motility is controlled and provides evidence that the molecular mechanism underlying Dock180-related protein function is evolutionarily conserved. INTRODUCTIONIn eukaryotes, cell migration is essential for many biological processes such as embryonic development and tissue renewal and in humans it is also linked to numerous pathologies including cancer. Cells are set in motion through reorganization of the actin cytoskeleton that creates cytoplasmic protrusions and promotes forward movement. Members of the Rac subfamily of Rho small GTPases are key regulators of cytoskeletal dynamics in virtually all eukaryotes. Activated Rac proteins relay directional signals from the leading edge of migrating cells to downstream effectors such as SCAR/WAVE and WASP proteins that mediate F-actin polymerization and power cell motility (Jaffe and Hall, 2005;Ridley, 2006;Charest and Firtel, 2007;Kolsch et al., 2008;Ladwein and Rottner, 2008). Despite their importance, the upstream signaling mechanisms that mediate Rac activation during cell migration are still unclear.The activity of the small GTPases is regulated through a GDP/GTP exchange mechanism that is catalyzed by the guanine nucleotide exchange factors (GEF), GTPase-activating proteins (GAPs), and guanine nucleotide-dissociation inhibitors (GDIs). GEFs activate GTPases by catalyzing the dissociation of GDP from the protein, thereby allowing the binding of GTP and their switch to an active state. Members of the classical Dbl homology-pleckstrin homology (DH-PH) domain-containing family were thought to be the universal activators of Rho GTPases until the CZH (CDM-zizimin homology) family of unconventional Rho-GEFs was discovered (Côté and Vuori, 2002;Meller et al., 2005;Côté and Vuori, 2007). In the CZH proteins, a CZH2 domain, rather than a DH domain, interacts wi...

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“…Nearly every DD protein (Vlahou and Rivero 2006) has an ortholog in both DF and PP (Supplemental Table S5.10). Only the family of Rho GTPases seems to have diversified independently in the three species.…”

Section: Cytoskeleton and Movementmentioning

confidence: 99%

Phylogeny-wide analysis of social amoeba genomes highlights ancient origins for complex intercellular communication

Heidel¹,

Lawal²,

Felder³

et al. 2011

Genome Res.

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150

161

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Dictyostelium discoideum (DD), an extensively studied model organism for cell and developmental biology, belongs to the most derived group 4 of social amoebas, a clade of altruistic multicellular organisms. To understand genome evolution over long time periods and the genetic basis of social evolution, we sequenced the genomes of Dictyostelium fasciculatum (DF ) and Polysphondylium pallidum (PP), which represent the early diverging groups 1 and 2, respectively. In contrast to DD, PP and DF have conventional telomere organization and strongly reduced numbers of transposable elements. The number of proteincoding genes is similar between species, but only half of them comprise an identifiable set of orthologous genes. In general, genes involved in primary metabolism, cytoskeletal functions and signal transduction are conserved, while genes involved in secondary metabolism, export, and signal perception underwent large differential gene family expansions. This most likely signifies involvement of the conserved set in core cell and developmental mechanisms, and of the diverged set in niche-and species-specific adaptations for defense and food, mate, and kin selection. Phylogenetic dating using a concatenated data set and extensive loss of synteny indicate that DF, PP, and DD split from their last common ancestor at least 0.6 billion years ago.[Supplemental material is available for this article.]The central and most fascinating problem in biology is how natural selection has acted on random changes in the genomes of individuals to generate the immense range and complexity of extinct and extant living forms. However, understanding the relationship between genotypic and phenotypic change on a genomewide scale is complicated by the large number of loci involved and the range of phenotypic change. Comparative genomics is the tool of choice to define common gene sets and the first occurrence of genetic changes that may have caused phenotypic innovation. Genetic manipulation of altered genes can then reveal whether the genomic change was causal to the phenotypic alteration.The social amoeba Dictyostelium discoideum (DD) is a widely used model system for studying a range of problems in cell and developmental biology and more recently the evolution of social behavior and multicellularity.

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Rho GTPase signaling in Dictyostelium discoideum: Insights from the genome

Cited by 70 publications

References 70 publications

Dictyostelium MEGAPs: F-BAR domain proteins that regulate motility and membrane tubulation in contractile vacuoles

Dictyostelium MEGAPs: F-BAR domain proteins that regulate motility and membrane tubulation in contractile vacuoles

DictyosteliumDock180-related RacGEFs Regulate the Actin Cytoskeleton during Cell Motility

Phylogeny-wide analysis of social amoeba genomes highlights ancient origins for complex intercellular communication

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