title: A new member of the Rho family, Rnd1, promotes disassembly of actin filament structures and loss of cell adhesion.
abstract: Members of the Rho GTPase family regulate the organization of the actin cytoskeleton in response to extracellular growth factors. We have identified three proteins that form a distinct branch of the Rho family: Rnd1, expressed mostly in brain and liver; Rnd2, highly expressed in testis; and Rnd3/RhoE, showing a ubiquitous low expression. At the subcellular level, Rnd1 is concentrated at adherens junctions both in confluent fibroblasts and in epithelial cells. Rnd1 has a low affinity for GDP and spontaneously exchanges nucleotide rapidly in a physiological buffer. Furthermore, Rnd1 lacks intrinsic GTPase activity suggesting that in vivo, it might be constitutively in a GTP-bound form. Expression of Rnd1 or Rnd3/RhoE in fibroblasts inhibits the formation of actin stress fibers, membrane ruffles, and integrin-based focal adhesions and induces loss of cell-substrate adhesion leading to cell rounding (hence Rnd for "round"). We suggest that these proteins control rearrangements of the actin cytoskeleton and changes in cell adhesion.
authors.affiliation: Medical Research Council Laboratory for Molecular Cell Biology, Cancer Research Campaign Oncogene and Signal Transduction Group and Department of Biochemistry, University College London, London WC1E 7BT, United Kingdom. chardin@cc.ucsf.edu
authors.forename: C D
authors.initials: CD
authors.lastname: Nobes
authors.forename: I
authors.initials: I
authors.lastname: Lauritzen
authors.forename: M G
authors.initials: MG
authors.lastname: Mattei
authors.forename: S
authors.initials: S
authors.lastname: Paris
authors.forename: A
authors.initials: A
authors.lastname: Hall
authors.forename: P
authors.initials: P
authors.lastname: Chardin
mesh_terms: D016475:3T3 Cells; D000199:Actins / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D002448:Cell Adhesion / Q000502:physiology*; D002874:Chromosome Mapping; D002877:Chromosomes, Human; D002881:Chromosomes, Human, Pair 12; D002886:Chromosomes, Human, Pair 17; D018076:DNA, Complementary; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015723:Gene Library; D006801:Humans; D017403:In Situ Hybridization; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000378:metabolism; D020741:rho GTP-Binding Proteins
chemical_list: D000199:Actins; D018076:DNA, Complementary; C491772:RND1 protein, human; D011994:Recombinant Proteins; C111871:Rnd1 protein, mouse; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020741:rho GTP-Binding Proteins