RHO GTPase cycle

Covill-Cooke C, Toncheva VS, Drew J, Birsa N, López-Doménech G, Kittler JT. Peroxisomal fission is modulated by the mitochondrial Rho-GTPases, Miro1 and Miro2. EMBO Rep. 2020 Feb 05;21(2):e49865. PMID: 31894645; PMCID: PMC7001505.; de Curtis I. The Rac3 GTPase in Neuronal Development, Neurodevelopmental Disorders, and Cancer. Cells. 2019 Sep 11;8(9). PMID: 31514269; PMCID: PMC6770886.; Mouly L, Gilhodes J, Lemarié A, Cohen-Jonathan Moyal E, Toulas C, Favre G, Sordet O, Monferran S. The RND1 Small GTPase: Main Functions and Emerging Role in Oncogenesis. Int J Mol Sci. 2019 Jul 24;20(15). PMID: 31344837; PMCID: PMC6696182.; Kalpachidou T, Spiecker L, Kress M, Quarta S. Rho GTPases in the Physiology and Pathophysiology of Peripheral Sensory Neurons. Cells. 2019 Jun 15;8(6). PMID: 31208035; PMCID: PMC6627758.; Pichaud F, Walther RF, Nunes de Almeida F. Regulation of Cdc42 and its effectors in epithelial morphogenesis. J Cell Sci. 2019 May 21;132(10). doi: 10.1242/jcs.217869. PMID: 31113848.; Xiao XH, Lv LC, Duan J, Wu YM, He SJ, Hu ZZ, Xiong LX. Regulating Cdc42 and Its Signaling Pathways in Cancer: Small Molecules and MicroRNA as New Treatment Candidates. Molecules. 2018 Mar 29;23(4). PMID: 29596304; PMCID: PMC6017947.; Guan X, Chen S, Zhao Y. The role of RhoC in malignant tumor invasion, metastasis and targeted therapy. Histol Histopathol. 2018 Mar;33(3):255–60. doi: 10.14670/hh-11-915. PMID: 28664531.; Castro IG, Richards DM, Metz J, Costello JL, Passmore JB, Schrader TA, Gouveia A, Ribeiro D, Schrader M. A role for Mitochondrial Rho GTPase 1 (MIRO1) in motility and membrane dynamics of peroxisomes. Traffic. 2018 Mar;19(3):229–42. PMID: 29364559; PMCID: PMC5888202.; Acevedo A, González-Billault C. Crosstalk between Rac1-mediated actin regulation and ROS production. Free Radic Biol Med. 2018 Feb 20;116():101–13. doi: 10.1016/j.freeradbiomed.2018.01.008. PMID: 29330095.; Aspenström P. Fast-cycling Rho GTPases. Small GTPases. 2018 Jan 29;11(4):248–55. doi: 10.1080/21541248.2017.1391365.; Okumoto K, Ono T, Toyama R, Shimomura A, Nagata A, Fujiki Y. New splicing variants of mitochondrial Rho GTPase-1 (Miro1) transport peroxisomes. J Cell Biol. 2018 Feb 05;217(2):619–33. PMID: 29222186; PMCID: PMC5800816.; Liu WN, Yan M, Chan AM. A thirty-year quest for a role of R-Ras in cancer: from an oncogene to a multitasking GTPase. Cancer Lett. 2017 Sep 10;403():59–65. doi: 10.1016/j.canlet.2017.06.003. PMID: 28610953.; Fort P, Blangy A. The Evolutionary Landscape of Dbl-Like RhoGEF Families: Adapting Eukaryotic Cells to Environmental Signals. Genome Biol Evol. 2017 Jun 01;9(6):1471–86. PMID: 28541439; PMCID: PMC5499878.; Egorov MV, Polishchuk RS. Emerging role of Cdc42-specific guanine nucleotide exchange factors as regulators of membrane trafficking in health and disease. Tissue Cell. 2017 Apr;49(2 Pt A):157–62. doi: 10.1016/j.tice.2016.10.002. PMID: 28029388.; Woods B, Lew DJ. Polarity establishment by Cdc42: Key roles for positive feedback and differential mobility. Small GTPases. 2017 Mar 30;10(2):130–7. doi: 10.1080/21541248.2016.1275370.; Vega FM, Ridley AJ. The RhoB small GTPase in physiology and disease. Small GTPases. 2016 Nov 22;9(5):384–93. doi: 10.1080/21541248.2016.1253528.; Haga RB, Ridley AJ. Rho GTPases: Regulation and roles in cancer cell biology. Small GTPases. 2016 Sep 26;7(4):207–21. doi: 10.1080/21541248.2016.1232583.; Amin E, Jaiswal M, Derewenda U, Reis K, Nouri K, Koessmeier KT, Aspenström P, Somlyo AV, Dvorsky R, Ahmadian MR. Deciphering the Molecular and Functional Basis of RHOGAP Family Proteins: A SYSTEMATIC APPROACH TOWARD SELECTIVE INACTIVATION OF RHO FAMILY PROTEINS. J Biol Chem. 2016 Sep 23;291(39):20353–71. PMID: 27481945; PMCID: PMC5034035.; Olson MF. Rho GTPases, their post-translational modifications, disease-associated mutations and pharmacological inhibitors. Small GTPases. 2016 Aug 22;9(3):203–15. doi: 10.1080/21541248.2016.1218407.; Marei H, Malliri A. GEFs: Dual regulation of Rac1 signaling. Small GTPases. 2016 Jun 17;8(2):90–9. doi: 10.1080/21541248.2016.1202635.; Hodge RG, Ridley AJ. Regulating Rho GTPases and their regulators. Nature Reviews Molecular Cell Biology. 2016 Jun 15;17(8):496–510. doi: 10.1038/nrm.2016.67.; Ji W, Rivero F. Atypical Rho GTPases of the RhoBTB Subfamily: Roles in Vesicle Trafficking and Tumorigenesis. Cells. 2016 Jun 14;5(2). PMID: 27314390; PMCID: PMC4931677.; Devine MJ, Birsa N, Kittler JT. Miro sculpts mitochondrial dynamics in neuronal health and disease. Neurobiol Dis. 2016 Jun;90():27–34. doi: 10.1016/j.nbd.2015.12.008. PMID: 26707701.; Shi T, Li G, Xiao H. The Role of RhoJ in Endothelial Cell Biology and Tumor Pathology. BioMed Research International. 2016;2016():1–9. doi: 10.1155/2016/6386412.; Faure S, Fort P. Atypical RhoV and RhoU GTPases control development of the neural crest. Small GTPases. 2015 Oct 02;6(4):174–7. doi: 10.1080/21541248.2015.1025943.; Ridley AJ. Rho GTPase signalling in cell migration. Current Opinion in Cell Biology. 2015 Oct;36():103–12. doi: 10.1016/j.ceb.2015.08.005.; Donnelly SK, Bravo-Cordero JJ, Hodgson L. Rho GTPase isoforms in cell motility: Don't fret, we have FRET. Cell Adhesion & Migration. 2014 Oct 31;8(6):526–34. doi: 10.4161/cam.29712.; Aspenström P. Atypical Rho GTPases RhoD and Rif integrate cytoskeletal dynamics and membrane trafficking. Biol Chem. 2014 May;395(5):477–84. doi: 10.1515/hsz-2013-0296. PMID: 24622787.; Klosowiak JL, Focia PJ, Chakravarthy S, Landahl EC, Freymann DM, Rice SE. Structural coupling of the EF hand and C-terminal GTPase domains in the mitochondrial protein Miro. EMBO Reports. 2013 Sep 27;14(11):968–74. doi: 10.1038/embor.2013.151.; Lemichez E, Aktories K. Hijacking of Rho GTPases during bacterial infection. Exp Cell Res. 2013 Sep 10;319(15):2329–36. doi: 10.1016/j.yexcr.2013.04.021. PMID: 23648569.; Troeger A, Williams DA. Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders. Experimental Cell Research. 2013 Sep;319(15):2375–83. doi: 10.1016/j.yexcr.2013.07.002.; Schwarz TL. Mitochondrial Trafficking in Neurons. Cold Spring Harbor Perspectives in Biology. 2013 Jun 01;5(6):a011304. doi: 10.1101/cshperspect.a011304.; Lessey EC, Guilluy C, Burridge K. From mechanical force to RhoA activation. Biochemistry. 2012 Sep 25;51(38):7420–32. PMID: 22931484; PMCID: PMC3567302.; Fan L, Mellor H. The small Rho GTPase Rif and actin cytoskeletal remodelling. Biochem Soc Trans. 2012 Feb;40(1):268–72. doi: 10.1042/bst20110625. PMID: 22260703.; Leszczynska K, Kaur S, Wilson E, Bicknell R, Heath VL. The role of RhoJ in endothelial cell biology and angiogenesis. Biochem Soc Trans. 2011 Dec;39(6):1606–11. doi: 10.1042/bst20110702. PMID: 22103495.; Gad AK, Aspenström P. Rif proteins take to the RhoD: Rho GTPases at the crossroads of actin dynamics and membrane trafficking. Cell Signal. 2010 Feb;22(2):183–9. doi: 10.1016/j.cellsig.2009.10.001. PMID: 19818399.; Berthold J, Schenkova K, Rivero F. Rho GTPases of the RhoBTB subfamily and tumorigenesis. Acta Pharmacol Sin. 2008 Mar;29(3):285–95. doi: 10.1111/j.1745-7254.2008.00773.x. PMID: 18298893.; Suzuki H, Oda H. The atypical small GTPase RhoH : a novel role in T cell development. Nihon Rinsho Meneki Gakkai Kaishi. 2008 Feb;31(1):37–46. doi: 10.2177/jsci.31.37. PMID: 18311041.; Tcherkezian J, Lamarche-Vane N. Current knowledge of the large RhoGAP family of proteins. Biol Cell. 2007 Feb;99(2):67–86. doi: 10.1042/bc20060086. PMID: 17222083.; Boureux A, Vignal E, Faure S, Fort P. Evolution of the Rho family of ras-like GTPases in eukaryotes. Mol Biol Evol. 2007 Jan;24(1):203–16. PMID: 17035353; PMCID: PMC2665304.; Meller N, Merlot S, Guda C. CZH proteins: a new family of Rho-GEFs. J Cell Sci. 2005 Nov 01;118(Pt 21):4937–46. doi: 10.1242/jcs.02671. PMID: 16254241.; Jaffe AB, Hall A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol. 2005;21():247–69. doi: 10.1146/annurev.cellbio.21.020604.150721. PMID: 16212495.; Dransart E, Olofsson B, Cherfils J. RhoGDIs revisited: novel roles in Rho regulation. Traffic. 2005 Nov;6(11):957–66. doi: 10.1111/j.1600-0854.2005.00335.x. PMID: 16190977.; Cheng J, Wang H, Guggino WB. Regulation of Cystic Fibrosis Transmembrane Regulator Trafficking and Protein Expression by a Rho Family Small GTPase TC10. Journal of Biological Chemistry. 2005 Feb;280(5):3731–9. doi: 10.1074/jbc.m410026200.; Randazzo PA. RhoD, Src, and hDia2C in endosome motility. Dev Cell. 2003 Mar;4(3):287–8. doi: 10.1016/s1534-5807(03)00067-4. PMID: 12636908.; Van Aelst L, D'Souza-Schorey C. Rho GTPases and signaling networks. Genes Dev. 1997 Sep 15;11(18):2295–322. doi: 10.1101/gad.11.18.2295. PMID: 9308960.

Metabolites

H2O

Formula: H2O (18.0105642)

CAS ID: 7732-18-5

GTP(4-)

Formula: C10H12N5O14P3 (518.9593642)

CAS ID: 86527-72-2



Enzyme

EC Number name full name note
3.6.5.2 small monomeric GTPase GTP phosphohydrolase (cell-regulating)
5.6.1.6 channel-conductance-controlling ATPase ATP phosphohydrolase (channel-conductance-controlling)


Proteins

Protein ID name full name