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Rnd Proteins: A New Family of Rho-Related Proteins That Interfere with the Assembly of Filamentous Actin Structures and Cell Adhesion

  • Pierre Chardin
Part of the Progress in Molecular and Subcellular Biology book series (PMSB, volume 22)

Abstract

Rho family proteins control actin organization. The Rnd proteins form a distinct branch of the Rho family: Rnd1 is expressed mostly in brain and liver, Rnd2 is highly expressed in testis and Rnd3 shows a ubiquitous, very low expression. In brain, Rnd1 is found in specialized neurons, mainly in the cortex, hippocampus and substantia nigra. Rnd1 exchanges GTP rapidly, has a low affinity for GDP, and lacks intrinsic GTPase activity, suggesting that in the cell it is constitutively in the GTP-bound form. Expression of Rnd1 in Swiss 3T3 fibroblasts inhibits the formation of actin stress fibers and induces a loss of focal adhesions and cell/cell contacts, leading to cell rounding (hence Rnd for “round”). In Swiss 3T3 fibroblasts and MDCK cells, Rnd1 localizes to adherens junctions. Thus, Rnd proteins are involved in rearrangements of the actin cytoskeleton and changes in cell adhesion that might play essential roles in cell migration and tumor invasion.

Keywords

Stress Fiber Actin Stress Fiber Phosphorylate Myosin Light Chain Stress Fiber Formation Myosin Light Chain Phosphatase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Aberle H, Bierkamp C, Torchard D et al. (1995) The human plakoglobin gene localizes on chromosome 17 q21 and is subjected to loss of heterozygosity in breast and ovarian cancers. Proc Natl Acad Sci USA 92:6384–6388PubMedCrossRefGoogle Scholar
  2. Adamson P, Paterson HF, Hall A (1992) Intracellular localization of the p21Rho proteins. J Cell Biol 119:617–627PubMedCrossRefGoogle Scholar
  3. Aktories K, Just I (1995) In vitro ADP-ribosylation of Rho by bacterial ADP-ribosyl transferases. Methods in enzymology, 256, part B. Academic Press, New York, pp 184–195Google Scholar
  4. Bar-Sagi D, Feramisco JR (1986) Induction of membrane ruffling and fluid-phase pinocytosis in quiescent fibroblasts by Ras proteins. Science 233:1061–1068PubMedCrossRefGoogle Scholar
  5. Ben-Ze’ev A (1997) Cytoskeletal and adhesion proteins as tumor suppressors. Curr Opin Cell Biol 9:99–108PubMedCrossRefGoogle Scholar
  6. Birchmeier W, Berhens J (1994) Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta 1198:11–26PubMedGoogle Scholar
  7. Bokoch GM, Bohl BP, Chuang TH (1994) Guanine nucleotide exchange regulates membrane translocation of rac/Rho GTP-binding proteins. J Biol Chem 269:31674–31679PubMedGoogle Scholar
  8. Chardin P, Boquet P, Madaule P, Popoff MR, Rubin EJ, Gill DM (1989) The mammalian G protein RhoC is ADP-ribosylated by clostridium botulinum exoenzyme C3 and affects actin microfilaments in Vero cells. EMBO J 8:1087–1092PubMedGoogle Scholar
  9. Dallery-Prudhomme E, Roumier C, Denis C, Preudhomme C, Kerckaert JP, Galiegue-Zouitina S (1997) Genomic structure and assignment of the RhoH/TTF small GTPase gene (ARHH) to 4p13 by in situ hybridization. Genomics 43:89–94PubMedCrossRefGoogle Scholar
  10. Der CJ, Finkel T, Cooper GM (1996) Biological and biochemical properties of human H-ras genes mutated at codon 61. Cell 44:167–176CrossRefGoogle Scholar
  11. Foster R, Hu K-Q, Lu Y, Nolan KM, Thissen J, Settleman J (1996) Identification of a novel human Rho protein with unusual properties: GTPase deficiency and in vivo farnesylation. Mol Cell Biol 16:2689–2699PubMedGoogle Scholar
  12. Habets GGM, Scholte EHM, Zuydgeest D, Van der Kammen RA, Stam JC, Berns A, Collard JG (1994) Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins. Cell 77:539–547CrossRefGoogle Scholar
  13. Hirshberg M, Stockley RW, Dodson G, Webb MR (1997) The crystal structure of human rad, a member of the rho-family complexed with a GTP analogue. Nat Str Biol 4:147–151CrossRefGoogle Scholar
  14. Huber LA, Ullrich O, Takai Y et al. (1994) Mapping of Ras-related GTP-binding proteins by GTP overlay following two-dimensional gel electrophoresis. Proc Natl Acad Sci USA 91:7874–7878PubMedCrossRefGoogle Scholar
  15. Hughes PE, Renshaw MW, Pfaff M et al. (1997) Suppression of integrin activation: a novel function of a Ras/raf-initiated MAP Kinase pathway. Cell 88:521–530PubMedCrossRefGoogle Scholar
  16. John J, Frech M, Wittinghofer A (1988) Biochemical properties of H-Ras encoded p21 mutants and mechanism of the autophosphorylation reaction J Biol Chem 263:11792–11799Google Scholar
  17. Kimura K, Ito M, Amano M et al. (1996) Regulation of myosin phosphatase by Rho and Rhoassociated kinase. Science 273:245–248PubMedCrossRefGoogle Scholar
  18. Murphy C, Saffrich R, Grummt M, Gournier H, Rybin V, Rubino M, Auvinen P, Lutcke A, Parton RG, Zerial M (1996) Endosome dynamics regulated by a Rho protein. Nature 384:427–432PubMedCrossRefGoogle Scholar
  19. Nobes CD, Hall A (1995) Rho, rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81:53–62PubMedCrossRefGoogle Scholar
  20. Nobes CD, Lauritzen I, Mattei M-G, Paris S, Hall A, Chardin P (1998) A new member of the Rho family, Rndl, promotes disassembly of actin filament structures and loss of cell adhesion. J Cell Biol 141:187–197PubMedCrossRefGoogle Scholar
  21. Olson MF, Ashworth A, Hall A (1995) An essential role for Rho, rac, and Cdc42 GTPases in cell cycle progression through G1. Science 269:1270–1272PubMedCrossRefGoogle Scholar
  22. Pai E, Krengel U, Petsko GA et al. (1990) Refined crystal structure of the triphosphate conformation of H-ras p21 at 1.35 A resolution: implications for the mechanism of GTP hydrolysis. EMBO J 9:2351–2359PubMedGoogle Scholar
  23. Prendergast GC, Davide JP, deSolms SJ et al. (1994) Farnesyltransferase inhibition causes morphological reversion of Ras-transformed cells by a complex mechanism that involves regulation of the actin cytoskeleton. Mol Cell Biol 14:4193–4202PubMedGoogle Scholar
  24. Qiu R.-G, Chen J, Kirn D, McCormick F, Symons M (1995a) An essential role for rac in Ras transformation. Nature 374:457–459CrossRefGoogle Scholar
  25. Qiu R-G, Chen J, McCormick F, Symons M (1995b) A role for Rho in Ras transformation. Proc Natl Acad Sci USA 92:11781–11785CrossRefGoogle Scholar
  26. Ridley AJ, Hall A (1992) The small GTP-binding protein Rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70:389–399PubMedCrossRefGoogle Scholar
  27. Ridley AJ, Patterson HF, Johnston CL, Diekmann D, Hall A (1992) The small GTP-binding protein rac regulates growth factorinduced membrane ruffling. Cell 70:401–410PubMedCrossRefGoogle Scholar
  28. Russell LD (1993) In: Russell LD, Griswold MD (eds) The sertoli cell Cache River Press, FloridaGoogle Scholar
  29. Smith TM, Lee MK, Szabo CI, Jerome N et al. (1996) Complete genomic sequence and analysis of 117kb of human DNA containing the gene BRCA1. Genome Res 6:1029–1049PubMedCrossRefGoogle Scholar
  30. Symons M (1996) Rho family GTPases: the cytoskeleton and beyond. Trends Biochem Sci 21:178–181PubMedGoogle Scholar
  31. Tsukita S, Yonemura S, Tsukita S (1997) ERM family: from cytoskeleton to signal transduction. Curr Opin Cell Biol 9:70–75PubMedCrossRefGoogle Scholar
  32. Van Aelst L, D’Souza-Schorey C (1997) Rho GTPases and signaling networks. Genes Dev 11:2295–2322Google Scholar
  33. Wei Y, Zhang Y, Derewanda U, Liu X, Minor W, Nakamoto RK, Somlyo AV, Somlyo AP, Derewanda ZS (1997) Crystal structure of RhoA-GDP and its functional implications. Nat Str Biol 4:699–703CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • Pierre Chardin
    • 1
    • 2
  1. 1.Cancer Center UCSFSan FranciscoUSA
  2. 2.Institute de PharmacologieCNRS UPR 411ValbonneFrance

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