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. 2004 Jan 15;377(Pt 2):327–337. doi: 10.1042/BJ20031041

Rho GTPases have diverse effects on the organization of the actin filament system.

Pontus Aspenström 1, Asa Fransson 1, Jan Saras 1
PMCID: PMC1223866  PMID: 14521508

Abstract

The Rho GTPases are related to the Ras proto-oncogenes and consist of 22 family members. These proteins have important roles in regulating the organization of the actin filament system, and thereby the morphogenesis of vertebrate cells as well as their ability to migrate. In an effort to compare the effects of all members of the Rho GTPase family, active Rho GTPases were transfected into porcine aortic endothelial cells and the effects on the actin filament system were monitored. Cdc42, TCL (TC10-like), Rac1-Rac3 and RhoG induced the formation of lamellipodia, whereas Cdc42, Rac1 and Rac2 also induced the formation of thick bundles of actin filaments. In contrast, transfection with TC10 or Chp resulted in the formation of focal adhesion-like structures, whereas Wrch-1 induced long and thin filopodia. Transfection with RhoA, RhoB or RhoC induced the assembly of stress fibres, whereas Rnd1-Rnd3 resulted in the loss of stress fibres, but this effect was associated with the formation of actin- and ezrin-containing dorsal microvilli. Cells expressing RhoD and Rif had extremely long and flexible filopodia. None of the RhoBTB or Miro GTPases had any major influence on the organization of the actin filament system; instead, RhoBTB1 and RhoBTB2 were present in vesicular structures, and Miro-1 and Miro-2 were present in mitochondria. Collectively, the data obtained in this study to some extent confirm earlier observations, but also allow the identification of previously undetected roles of the different members of the Rho GTPases.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abe Tomoyuki, Kato Masayoshi, Miki Hiroaki, Takenawa Tadaomi, Endo Takeshi. Small GTPase Tc10 and its homologue RhoT induce N-WASP-mediated long process formation and neurite outgrowth. J Cell Sci. 2003 Jan 1;116(Pt 1):155–168. doi: 10.1242/jcs.00208. [DOI] [PubMed] [Google Scholar]
  2. Algrain M., Turunen O., Vaheri A., Louvard D., Arpin M. Ezrin contains cytoskeleton and membrane binding domains accounting for its proposed role as a membrane-cytoskeletal linker. J Cell Biol. 1993 Jan;120(1):129–139. doi: 10.1083/jcb.120.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aronheim A., Broder Y. C., Cohen A., Fritsch A., Belisle B., Abo A. Chp, a homologue of the GTPase Cdc42Hs, activates the JNK pathway and is implicated in reorganizing the actin cytoskeleton. Curr Biol. 1998 Oct 8;8(20):1125–1128. doi: 10.1016/s0960-9822(98)70468-3. [DOI] [PubMed] [Google Scholar]
  4. Aspenström P. A Cdc42 target protein with homology to the non-kinase domain of FER has a potential role in regulating the actin cytoskeleton. Curr Biol. 1997 Jul 1;7(7):479–487. doi: 10.1016/s0960-9822(06)00219-3. [DOI] [PubMed] [Google Scholar]
  5. Aspenström P., Lindberg U., Hall A. Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the immunodeficiency disorder Wiskott-Aldrich syndrome. Curr Biol. 1996 Jan 1;6(1):70–75. doi: 10.1016/s0960-9822(02)00423-2. [DOI] [PubMed] [Google Scholar]
  6. Barbacid M. ras genes. Annu Rev Biochem. 1987;56:779–827. doi: 10.1146/annurev.bi.56.070187.004023. [DOI] [PubMed] [Google Scholar]
  7. Bishop A. L., Hall A. Rho GTPases and their effector proteins. Biochem J. 2000 Jun 1;348(Pt 2):241–255. [PMC free article] [PubMed] [Google Scholar]
  8. Boettger-Tong H. L., Agulnik A. I., Ty T. I., Bishop C. E. Transposition of RhoA to the murine Y chromosome. Genomics. 1998 Apr 15;49(2):180–187. doi: 10.1006/geno.1998.5219. [DOI] [PubMed] [Google Scholar]
  9. Bretscher A., Chambers D., Nguyen R., Reczek D. ERM-Merlin and EBP50 protein families in plasma membrane organization and function. Annu Rev Cell Dev Biol. 2000;16:113–143. doi: 10.1146/annurev.cellbio.16.1.113. [DOI] [PubMed] [Google Scholar]
  10. Cannon J. L., Labno C. M., Bosco G., Seth A., McGavin M. H., Siminovitch K. A., Rosen M. K., Burkhardt J. K. Wasp recruitment to the T cell:APC contact site occurs independently of Cdc42 activation. Immunity. 2001 Aug;15(2):249–259. doi: 10.1016/s1074-7613(01)00178-9. [DOI] [PubMed] [Google Scholar]
  11. Caron Emmanuelle. Regulation of Wiskott-Aldrich syndrome protein and related molecules. Curr Opin Cell Biol. 2002 Feb;14(1):82–87. doi: 10.1016/s0955-0674(01)00298-8. [DOI] [PubMed] [Google Scholar]
  12. Collins T., Stone J. R., Williams A. J. All in the family: the BTB/POZ, KRAB, and SCAN domains. Mol Cell Biol. 2001 Jun;21(11):3609–3615. doi: 10.1128/MCB.21.11.3609-3615.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dallery E., Galiègue-Zouitina S., Collyn-d'Hooghe M., Quief S., Denis C., Hildebrand M. P., Lantoine D., Deweindt C., Tilly H., Bastard C. TTF, a gene encoding a novel small G protein, fuses to the lymphoma-associated LAZ3 gene by t(3;4) chromosomal translocation. Oncogene. 1995 Jun 1;10(11):2171–2178. [PubMed] [Google Scholar]
  14. Edlund Sofia, Landström Maréne, Heldin Carl-Henrik, Aspenström Pontus. Transforming growth factor-beta-induced mobilization of actin cytoskeleton requires signaling by small GTPases Cdc42 and RhoA. Mol Biol Cell. 2002 Mar;13(3):902–914. doi: 10.1091/mbc.01-08-0398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ellis S., Mellor H. The novel Rho-family GTPase rif regulates coordinated actin-based membrane rearrangements. Curr Biol. 2000 Nov 2;10(21):1387–1390. doi: 10.1016/s0960-9822(00)00777-6. [DOI] [PubMed] [Google Scholar]
  16. Eriksson A., Siegbahn A., Westermark B., Heldin C. H., Claesson-Welsh L. PDGF alpha- and beta-receptors activate unique and common signal transduction pathways. EMBO J. 1992 Feb;11(2):543–550. doi: 10.1002/j.1460-2075.1992.tb05085.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Etienne-Manneville Sandrine, Hall Alan. Rho GTPases in cell biology. Nature. 2002 Dec 12;420(6916):629–635. doi: 10.1038/nature01148. [DOI] [PubMed] [Google Scholar]
  18. Foster R., Hu K. Q., Lu Y., Nolan K. M., Thissen J., Settleman J. Identification of a novel human Rho protein with unusual properties: GTPase deficiency and in vivo farnesylation. Mol Cell Biol. 1996 Jun;16(6):2689–2699. doi: 10.1128/mcb.16.6.2689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Fransson Asa, Ruusala Aino, Aspenström Pontus. Atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis. J Biol Chem. 2002 Dec 12;278(8):6495–6502. doi: 10.1074/jbc.M208609200. [DOI] [PubMed] [Google Scholar]
  20. Gampel A., Parker P. J., Mellor H. Regulation of epidermal growth factor receptor traffic by the small GTPase rhoB. Curr Biol. 1999 Sep 9;9(17):955–958. doi: 10.1016/s0960-9822(99)80422-9. [DOI] [PubMed] [Google Scholar]
  21. Gasman Stéphane, Kalaidzidis Yannis, Zerial Marino. RhoD regulates endosome dynamics through Diaphanous-related Formin and Src tyrosine kinase. Nat Cell Biol. 2003 Mar;5(3):195–204. doi: 10.1038/ncb935. [DOI] [PubMed] [Google Scholar]
  22. Gauthier-Rouvière C., Vignal E., Mériane M., Roux P., Montcourier P., Fort P. RhoG GTPase controls a pathway that independently activates Rac1 and Cdc42Hs. Mol Biol Cell. 1998 Jun;9(6):1379–1394. doi: 10.1091/mbc.9.6.1379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Guasch R. M., Scambler P., Jones G. E., Ridley A. J. RhoE regulates actin cytoskeleton organization and cell migration. Mol Cell Biol. 1998 Aug;18(8):4761–4771. doi: 10.1128/mcb.18.8.4761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lamaze C., Chuang T. H., Terlecky L. J., Bokoch G. M., Schmid S. L. Regulation of receptor-mediated endocytosis by Rho and Rac. Nature. 1996 Jul 11;382(6587):177–179. doi: 10.1038/382177a0. [DOI] [PubMed] [Google Scholar]
  25. Li Xiaoyu, Bu Xia, Lu Binfeng, Avraham Hava, Flavell Richard A., Lim Bing. The hematopoiesis-specific GTP-binding protein RhoH is GTPase deficient and modulates activities of other Rho GTPases by an inhibitory function. Mol Cell Biol. 2002 Feb;22(4):1158–1171. doi: 10.1128/MCB.22.4.1158-1171.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Liang Po-Huang, Ko Tzu-Ping, Wang Andrew H-J. Structure, mechanism and function of prenyltransferases. Eur J Biochem. 2002 Jul;269(14):3339–3354. doi: 10.1046/j.1432-1033.2002.03014.x. [DOI] [PubMed] [Google Scholar]
  27. Lin R., Bagrodia S., Cerione R., Manor D. A novel Cdc42Hs mutant induces cellular transformation. Curr Biol. 1997 Oct 1;7(10):794–797. doi: 10.1016/s0960-9822(06)00338-1. [DOI] [PubMed] [Google Scholar]
  28. Madaule P., Axel R. A novel ras-related gene family. Cell. 1985 May;41(1):31–40. doi: 10.1016/0092-8674(85)90058-3. [DOI] [PubMed] [Google Scholar]
  29. Moon Sun Young, Zheng Yi. Rho GTPase-activating proteins in cell regulation. Trends Cell Biol. 2003 Jan;13(1):13–22. doi: 10.1016/s0962-8924(02)00004-1. [DOI] [PubMed] [Google Scholar]
  30. Murphy C., Saffrich R., Grummt M., Gournier H., Rybin V., Rubino M., Auvinen P., Lütcke A., Parton R. G., Zerial M. Endosome dynamics regulated by a Rho protein. Nature. 1996 Dec 5;384(6608):427–432. doi: 10.1038/384427a0. [DOI] [PubMed] [Google Scholar]
  31. Neudauer C. L., Joberty G., Tatsis N., Macara I. G. Distinct cellular effects and interactions of the Rho-family GTPase TC10. Curr Biol. 1998 Oct 22;8(21):1151–1160. doi: 10.1016/s0960-9822(07)00486-1. [DOI] [PubMed] [Google Scholar]
  32. Nishizuka Makoto, Arimoto Emi, Tsuchiya Tomoko, Nishihara Tsutomu, Imagawa Masayoshi. Crucial role of TCL/TC10beta L, a subfamily of Rho GTPase, in adipocyte differentiation. J Biol Chem. 2003 Feb 9;278(17):15279–15284. doi: 10.1074/jbc.M211479200. [DOI] [PubMed] [Google Scholar]
  33. Nobes C. D., Hall A. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell. 1995 Apr 7;81(1):53–62. doi: 10.1016/0092-8674(95)90370-4. [DOI] [PubMed] [Google Scholar]
  34. Nobes C. D., Lauritzen I., Mattei M. G., Paris S., Hall A., Chardin P. A new member of the Rho family, Rnd1, promotes disassembly of actin filament structures and loss of cell adhesion. J Cell Biol. 1998 Apr 6;141(1):187–197. doi: 10.1083/jcb.141.1.187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Olofsson B. Rho guanine dissociation inhibitors: pivotal molecules in cellular signalling. Cell Signal. 1999 Aug;11(8):545–554. doi: 10.1016/s0898-6568(98)00063-1. [DOI] [PubMed] [Google Scholar]
  36. Preudhomme C., Roumier C., Hildebrand M. P., Dallery-Prudhomme E., Lantoine D., Laï J. L., Daudignon A., Adenis C., Bauters F., Fenaux P. Nonrandom 4p13 rearrangements of the RhoH/TTF gene, encoding a GTP-binding protein, in non-Hodgkin's lymphoma and multiple myeloma. Oncogene. 2000 Apr 13;19(16):2023–2032. doi: 10.1038/sj.onc.1203521. [DOI] [PubMed] [Google Scholar]
  37. Ramos Sonia, Khademi Farshad, Somesh Baggavalli P., Rivero Francisco. Genomic organization and expression profile of the small GTPases of the RhoBTB family in human and mouse. Gene. 2002 Oct 2;298(2):147–157. doi: 10.1016/s0378-1119(02)00980-0. [DOI] [PubMed] [Google Scholar]
  38. Ridley A. J. Rho GTPases and cell migration. J Cell Sci. 2001 Aug;114(Pt 15):2713–2722. doi: 10.1242/jcs.114.15.2713. [DOI] [PubMed] [Google Scholar]
  39. Ridley A. J. Rho family proteins: coordinating cell responses. Trends Cell Biol. 2001 Dec;11(12):471–477. doi: 10.1016/s0962-8924(01)02153-5. [DOI] [PubMed] [Google Scholar]
  40. Sasaki T., Takai Y. The Rho small G protein family-Rho GDI system as a temporal and spatial determinant for cytoskeletal control. Biochem Biophys Res Commun. 1998 Apr 28;245(3):641–645. doi: 10.1006/bbrc.1998.8253. [DOI] [PubMed] [Google Scholar]
  41. Schmidt Anja, Hall Alan. Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Dev. 2002 Jul 1;16(13):1587–1609. doi: 10.1101/gad.1003302. [DOI] [PubMed] [Google Scholar]
  42. Shields J. M., Pruitt K., McFall A., Shaub A., Der C. J. Understanding Ras: 'it ain't over 'til it's over'. Trends Cell Biol. 2000 Apr;10(4):147–154. doi: 10.1016/s0962-8924(00)01740-2. [DOI] [PubMed] [Google Scholar]
  43. Takai Y., Sasaki T., Matozaki T. Small GTP-binding proteins. Physiol Rev. 2001 Jan;81(1):153–208. doi: 10.1152/physrev.2001.81.1.153. [DOI] [PubMed] [Google Scholar]
  44. Tanabe K., Tachibana T., Yamashita T., Che Y. H., Yoneda Y., Ochi T., Tohyama M., Yoshikawa H., Kiyama H. The small GTP-binding protein TC10 promotes nerve elongation in neuronal cells, and its expression is induced during nerve regeneration in rats. J Neurosci. 2000 Jun 1;20(11):4138–4144. doi: 10.1523/JNEUROSCI.20-11-04138.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Tao W., Pennica D., Xu L., Kalejta R. F., Levine A. J. Wrch-1, a novel member of the Rho gene family that is regulated by Wnt-1. Genes Dev. 2001 Jul 15;15(14):1796–1807. doi: 10.1101/gad.894301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Vignal E., De Toledo M., Comunale F., Ladopoulou A., Gauthier-Rouvière C., Blangy A., Fort P. Characterization of TCL, a new GTPase of the rho family related to TC10 andCcdc42. J Biol Chem. 2000 Nov 17;275(46):36457–36464. doi: 10.1074/jbc.M003487200. [DOI] [PubMed] [Google Scholar]
  47. Wennerberg Krister, Ellerbroek Shawn M., Liu Rong-Yu, Karnoub Antoine E., Burridge Keith, Der Channing J. RhoG signals in parallel with Rac1 and Cdc42. J Biol Chem. 2002 Oct 9;277(49):47810–47817. doi: 10.1074/jbc.M203816200. [DOI] [PubMed] [Google Scholar]
  48. Wherlock Matthew, Mellor Harry. The Rho GTPase family: a Racs to Wrchs story. J Cell Sci. 2002 Jan 15;115(Pt 2):239–240. doi: 10.1242/jcs.115.2.239. [DOI] [PubMed] [Google Scholar]

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