title: Systematic functional analysis of the Ras GTPase family unveils a conserved network required for anterograde protein trafficking.
abstract: Phylogeny is often used to compare entire families of genes/proteins. We previously showed that classification of Caenorhabditis elegans Rho GTPases on the basis of their enzymatic properties was significantly different from sequence alignments. To further develop this concept, we have developed an integrated approach to classify C. elegans small GTPases based on functional data comprising affinity for GTP, sub-cellular localization, tissue distribution and silencing impact. This analysis led to establish a novel functional classification for small GTPases. To test the relevance of this classification in mammals, we focused our attention on the human orthologs of small GTPases from a specific group comprising arf-1.2, evl-20, arl-1, Y54E10BR.2, unc-108 and rab-7. We then tested their involvement in protein secretion and membrane traffic in mammalian systems. Using this approach we identify a novel network containing 18 GTPases, and 23 functionally interacting proteins, conserved between C. elegans and mammals, which is involved in membrane traffic and protein secretion.
authors.affiliation: Department of Surgery, McGill University, Montreal, QC, Canada.
authors.forename: Marie-Elaine
authors.initials: ME
authors.lastname: Caruso
authors.affiliation: Department of Surgery, McGill University, Montreal, QC, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Jenna
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: David L
authors.initials: DL
authors.lastname: Baillie
authors.affiliation: PerkinElmer, Waltham, MA, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Bossé
authors.affiliation: School of Biology & Environmental Science and Conway Institute of Biomolecular & Biomedical Research, University College Dublin (UCD), Dublin, Ireland.
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Simpson
authors.affiliation: Department of Surgery, McGill University, Montreal, QC, Canada.|INSERM U1242, COSS, Université de Rennes-1, CLCC Eugene Marquis, Rennes, France.|BMYscreen, Bordeaux, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Chevet
authors.affiliation: BMYscreen, Bordeaux, France.|INSERM U1218, CLCC Institut Bergonié, Bordeaux, France.
authors.forename: Saïd
authors.initials: S
authors.lastname: Taouji
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics / Q000502:physiology*; D040901:Proteomics / Q000379:methods; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D020559:Monomeric GTP-Binding Proteins; D018631:ras Proteins
keywords: Cell biology; GTPases; Global analysis; Membrane trafficking