Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
GTPases of the Rho family are molecular switches that play important roles in converting and amplifying external signals into cellular effects. Originally demonstrated to control the dynamics of the F-actin cytoskeleton, Rho GTPases have been implicated in many basic cellular processes that influence cell proliferation, differentiation, motility, adhesion, survival, or secretion. To elucidate the evolutionary history of the Rho family, we have analyzed over 20 species covering major eukaryotic clades from unicellular organisms to mammals, including platypus and opossum, and have reconstructed the ontogeny and the chronology of emergence of the different subfamilies. Our data establish that the 20 mammalian Rho members are structured into 8 subfamilies, among which Rac is the founder of the whole family. Rho, Cdc42, RhoUV, and RhoBTB subfamilies appeared before Coelomates and RhoJQ, Cdc42 isoforms, RhoDF, and Rnd emerged in chordates. In vertebrates, gene duplications and retrotranspositions increased the size of each chordate Rho subfamily, whereas RhoH, the last subfamily, arose probably by horizontal gene transfer. Rac1b, a Rac1 isoform generated by alternative splicing, emerged in amniotes, and RhoD, only in therians. Analysis of Rho mRNA expression patterns in mouse tissues shows that recent subfamilies have tissue-specific and low-level expression that supports their implication only in narrow time windows or in differentiated metabolic functions. These findings give a comprehensive view of the evolutionary canvas of the Rho family and provide guides for future structure and evolution studies of other components of Rho signaling pathways, in particular regulators of the RhoGEF family.
Abe,
Small GTPase Tc10 and its homologue RhoT induce N-WASP-mediated long process formation and neurite outgrowth.
2003, Pubmed
Abe,
Small GTPase Tc10 and its homologue RhoT induce N-WASP-mediated long process formation and neurite outgrowth.
2003,
Pubmed
Aktories,
Bacterial cytotoxins: targeting eukaryotic switches.
2005,
Pubmed
Altschul,
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
1997,
Pubmed
Andersen,
Generation of BALB-MuSV and Ha-MuSC by type C virus transduction of homologous transforming genes from different species.
1981,
Pubmed
Aronheim,
Chp, a homologue of the GTPase Cdc42Hs, activates the JNK pathway and is implicated in reorganizing the actin cytoskeleton.
1998,
Pubmed
Aspenström,
Rho GTPases have diverse effects on the organization of the actin filament system.
2004,
Pubmed
Berzat,
Transforming activity of the Rho family GTPase, Wrch-1, a Wnt-regulated Cdc42 homolog, is dependent on a novel carboxyl-terminal palmitoylation motif.
2005,
Pubmed
Blair,
Molecular phylogeny and divergence times of deuterostome animals.
2005,
Pubmed
Boon,
An anatomy of normal and malignant gene expression.
2002,
Pubmed
Bourne,
The GTPase superfamily: conserved structure and molecular mechanism.
1991,
Pubmed
Bucci,
Signal transduction gRABs attention.
2006,
Pubmed
Chambon,
Tail regression in Ciona intestinalis (Prochordate) involves a Caspase-dependent apoptosis event associated with ERK activation.
2002,
Pubmed
Chang,
Insulin signaling and the regulation of glucose transport.
2004,
Pubmed
Chartier,
Laminin-5-integrin interaction signals through PI 3-kinase and Rac1b to promote assembly of adherens junctions in HT-29 cells.
2006,
Pubmed
Chen,
Cdc42 is required for PIP(2)-induced actin polymerization and early development but not for cell viability.
2000,
Pubmed
Cho,
Generation of rac3 null mutant mice: role of Rac3 in Bcr/Abl-caused lymphoblastic leukemia.
2005,
Pubmed
Colicelli,
Human RAS superfamily proteins and related GTPases.
2004,
Pubmed
Corbetta,
Generation and characterization of Rac3 knockout mice.
2005,
Pubmed
Dallery-Prudhomme,
Genomic structure and assignment of the RhoH/TTF small GTPase gene (ARHH) to 4p13 by in situ hybridization.
1997,
Pubmed
Delsuc,
Tunicates and not cephalochordates are the closest living relatives of vertebrates.
2006,
Pubmed
de Toledo,
The GTP/GDP cycling of rho GTPase TCL is an essential regulator of the early endocytic pathway.
2003,
Pubmed
Donaldson,
Localization and function of Arf family GTPases.
2005,
Pubmed
Escher,
The Drosophila glucose transporter gene: cDNA sequence, phylogenetic comparisons, analysis of functional sites and secondary structures.
1999,
Pubmed
Felsenstein,
Inferring phylogenies from protein sequences by parsimony, distance, and likelihood methods.
1996,
Pubmed
Fiegen,
Alternative splicing of Rac1 generates Rac1b, a self-activating GTPase.
2004,
Pubmed
Field,
Signalling the genome: the Ras-like small GTPase family of trypanosomatids.
2005,
Pubmed
Freeman,
Rac "insert region" is a novel effector region that is implicated in the activation of NADPH oxidase, but not PAK65.
1996,
Pubmed
Fujita,
Rapostlin is a novel effector of Rnd2 GTPase inducing neurite branching.
2002,
Pubmed
Gasman,
RhoD regulates endosome dynamics through Diaphanous-related Formin and Src tyrosine kinase.
2003,
Pubmed
Graf,
Genetics of Xenopus laevis.
1991,
Pubmed
,
Xenbase
Gu,
ROP/RAC GTPase: an old new master regulator for plant signaling.
2004,
Pubmed
Hakeda-Suzuki,
Rac function and regulation during Drosophila development.
2002,
Pubmed
Hakem,
RhoC is dispensable for embryogenesis and tumor initiation but essential for metastasis.
2005,
Pubmed
Hall,
Rho GTPases and the actin cytoskeleton.
1998,
Pubmed
Hancock,
Ras plasma membrane signalling platforms.
2005,
Pubmed
Harbers,
Tag-based approaches for transcriptome research and genome annotation.
2005,
Pubmed
Hedges,
A molecular timescale of eukaryote evolution and the rise of complex multicellular life.
2004,
Pubmed
Hughes,
Phylogenies of developmentally important proteins do not support the hypothesis of two rounds of genome duplication early in vertebrate history.
1999,
Pubmed
Jaffe,
Rho GTPases: biochemistry and biology.
2005,
Pubmed
Jeanmougin,
Multiple sequence alignment with Clustal X.
1998,
Pubmed
Jordan,
Cloning of a novel human Rac1b splice variant with increased expression in colorectal tumors.
1999,
Pubmed
Li,
The hematopoiesis-specific GTP-binding protein RhoH is GTPase deficient and modulates activities of other Rho GTPases by an inhibitory function.
2002,
Pubmed
Liu,
RhoB is dispensable for mouse development, but it modifies susceptibility to tumor formation as well as cell adhesion and growth factor signaling in transformed cells.
2001,
Pubmed
Logan,
The Wnt signaling pathway in development and disease.
2004,
Pubmed
Lundquist,
Three C. elegans Rac proteins and several alternative Rac regulators control axon guidance, cell migration and apoptotic cell phagocytosis.
2001,
Pubmed
Madaule,
A novel ras-related gene family.
1985,
Pubmed
Marks,
Genomic organization and chromosomal location of murine Cdc42.
1996,
Pubmed
Matos,
Tumor-related alternatively spliced Rac1b is not regulated by Rho-GDP dissociation inhibitors and exhibits selective downstream signaling.
2003,
Pubmed
Meyer,
From 2R to 3R: evidence for a fish-specific genome duplication (FSGD).
2005,
Pubmed
Murphy,
Cellular functions of TC10, a Rho family GTPase: regulation of morphology, signal transduction and cell growth.
1999,
Pubmed
Ng,
Rac GTPases control axon growth, guidance and branching.
2002,
Pubmed
Page,
TreeView: an application to display phylogenetic trees on personal computers.
1996,
Pubmed
Panopoulou,
Timing and mechanism of ancient vertebrate genome duplications -- the adventure of a hypothesis.
2005,
Pubmed
Pemberton,
Mechanisms of receptor-mediated nuclear import and nuclear export.
2005,
Pubmed
Philippe,
Multigene analyses of bilaterian animals corroborate the monophyly of Ecdysozoa, Lophotrochozoa, and Protostomia.
2005,
Pubmed
Philips,
Ascidians as a vertebrate-like model organism for physiological studies of Rho GTPase signaling.
2003,
Pubmed
Pruyne,
Mechanisms of polarized growth and organelle segregation in yeast.
2004,
Pubmed
Reibel,
A hemopoietic specific gene encoding a small GTP binding protein is overexpressed during T cell activation.
1991,
Pubmed
Ridley,
Rho family proteins: coordinating cell responses.
2001,
Pubmed
Rivero,
The Dictyostelium discoideum family of Rho-related proteins.
2001,
Pubmed
Rivero,
Signal transduction pathways regulated by Rho GTPases in Dictyostelium.
2002,
Pubmed
Rozas,
DnaSP, DNA polymorphism analyses by the coalescent and other methods.
2003,
Pubmed
Saitou,
The neighbor-joining method: a new method for reconstructing phylogenetic trees.
1987,
Pubmed
Salas-Vidal,
Genomic annotation and expression analysis of the zebrafish Rho small GTPase family during development and bacterial infection.
2005,
Pubmed
Schnelzer,
Rac1 in human breast cancer: overexpression, mutation analysis, and characterization of a new isoform, Rac1b.
2000,
Pubmed
Seeburg,
Biological properties of human c-Ha-ras1 genes mutated at codon 12.
,
Pubmed
Seo,
Miniature genome in the marine chordate Oikopleura dioica.
2001,
Pubmed
Siripurapu,
DBC2 significantly influences cell-cycle, apoptosis, cytoskeleton and membrane-trafficking pathways.
2005,
Pubmed
Sugihara,
Rac1 is required for the formation of three germ layers during gastrulation.
1998,
Pubmed
Tanaka,
Control of reorganization of the actin cytoskeleton by Rho family small GTP-binding proteins in yeast.
1998,
Pubmed
Tao,
Wrch-1, a novel member of the Rho gene family that is regulated by Wnt-1.
2001,
Pubmed
Tarallo,
Time course of programmed cell death in Ciona intestinalis in relation to mitotic activity and MAPK signaling.
2004,
Pubmed
Valster,
Plant GTPases: the Rhos in bloom.
2000,
Pubmed
Velculescu,
Serial analysis of gene expression.
1995,
Pubmed
Venter,
The sequence of the human genome.
2001,
Pubmed
Vignal,
Characterization of TCL, a new GTPase of the rho family related to TC10 andCcdc42.
2000,
Pubmed
Vigorito,
Immunological function in mice lacking the Rac-related GTPase RhoG.
2004,
Pubmed
Wennerberg,
The Ras superfamily at a glance.
2005,
Pubmed
Wennerberg,
Rho-family GTPases: it's not only Rac and Rho (and I like it).
2004,
Pubmed
Wherlock,
The Rho GTPase family: a Racs to Wrchs story.
2002,
Pubmed
Wu,
The gamma-subunit of the coatomer complex binds Cdc42 to mediate transformation.
2000,
Pubmed
Zanata,
Antagonistic effects of Rnd1 and RhoD GTPases regulate receptor activity in Semaphorin 3A-induced cytoskeletal collapse.
2002,
Pubmed
Zipkin,
Role of a new Rho family member in cell migration and axon guidance in C. elegans.
1997,
Pubmed
