A new member of the Rho family, Rnd1, promotes disassembly of actin filament structures and loss of cell adhesion.
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.
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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
Lauritzen
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Mattei
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Paris
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Hall
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Chardin
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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
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