The interdependence of the Rho GTPases and apicobasal cell polarity

Small GTPases

Volumn 5, Issue 2, 2014, Pages

  Ann Mack, Natalie ^a   Georgiou, Marios ^a  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

Apicobasal; Cdc42; Epithelia; GTPases; Junction; Par; Polarity; Rac; Rho

Indexed keywords

PROTEIN CDC42; RAC PROTEIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; RHO KINASE;

APICAL MEMBRANE; APICOBASAL CELL POLARITY; ARTICLE; BIOLOGICAL PHENOMENA AND FUNCTIONS CONCERNING ORGAN SYSTEMS; CELL FUNCTION; CELL INTERACTION; CELL JUNCTION; CELL POLARITY; CELL TO CELL JUNCTION; FEEDBACK SYSTEM; HUMAN; INTRACELLULAR SIGNALING; LUMEN FORMATION; MOLECULAR INTERACTION; NONHUMAN; POLARITY PLASCTICITY; PROTEIN FUNCTION; TIGHT JUNCTION; TISSUE POLARITY;

EID: 84922241514     PISSN: 21541248     EISSN: 21541256     Source Type: Journal    
DOI: 10.4161/21541248.2014.973768     Document Type: Article

References (205)

1. Sahai E, Marshall CJ. RHO-GTPases and cancer. Nat Rev Cancer 2002; 2:133-42; PMID:12635176; http://dx.doi.org/10.1038/nrc725
2. Boulter E, Garcia-Mata R. Analysis of the role of RhoGDI1 and isoprenylation in the degradation of RhoGTPases. Methods Mol Biol 2012; 827:97-105; PMID:22144270; http://dx.doi.org/10.1007/978-1-61779-442-17
3. Castillo-Lluva S, Tatham MH, Jones RC, Jaffray EG, Edmondson RD, Hay RT, Malliri A. SUMOylation of the GTPase Rac1 is required for optimal cell migration. Nat Cell Biol 2010; 12:1078-85; PMID:20935639; http://dx.doi.org/10.1038/ncb2112
4. Castillo-Lluva S, Tan CT, Daugaard M, Sorensen PH, Malliri A. The tumour suppressor HACE1 controls cell migration by regulating Rac1 degradation. Oncogene 2013; 32:1735-42; PMID:22614015; http://dx.doi.org/10.1038/onc.2012.189
5. Lo P, Hawrot H, Georgiou M. Apicobasal polarity and its role in cancer progression. Biomol Concept 2012; 3:505-21; http://dx.doi.org/10.1515/bmc2012-0020
6. Wang AZ, Ojakian GK, Nelson WJ. Steps in the morphogenesis of a polarized epithelium. I. Uncoupling the roles of cell-cell and cell-substratum contact in establishing plasma membrane polarity in multicellular epithelial (MDCK) cysts. J Cell Sci 1990; 95 (Pt 1):137-51; PMID:2351699
7. Assemat E, Bazellieres E, Pallesi-Pocachard E, Le Bivic A, Massey-Harroche D. Polarity complex proteins. Biochim
8. Biophys Acta 2008; 1778:614-30; PMID:18005931; http://dx.doi.org/10.1016/j.bbamem.2007.08.029
9. Yamanaka T, Ohno S. Role of LglDlgScribble in the regulation of epithelial junction, polarity and growth. Front Biosci: J Virtual Libr 2008; 13:6693-707; PMID:18508688; http://dx.doi.org/10.2741/3182
10. Laprise P, Lau KM, Harris KP, Silva-Gagliardi NF, Paul SM, Beronja S, Beitel GJ, McGlade CJ, Tepass U. Yurt, Coracle, Neurexin IV and the Na(C),K (C)-ATPase form a novel group of epithelial polarity proteins. Nature 2009; 459:1141-5; PMID:19553998; http://dx.doi.org/10.1038/nature08067
11. Tepass U. FERM proteins in animal morphogenesis. Curr Opin Genet Dev 2009; 19:357-67; PMID: 19596566; http://dx.doi.org/10.1016/j.gde.2009.05.006
12. Benton R, St Johnston D. Drosophila PAR-1 and 143-3 inhibit BazookaPAR-3 to establish complementary cortical domains in polarized cells. Cell 2003; 115:691-704; PMID:14675534; http://dx.doi.org/10.1016/S0092-8674(03)00938-3
13. O’Brien LE, Jou TS, Pollack AL, Zhang Q, Hansen SH, Yurchenco P, Mostov KE. Rac1 orientates epithelial apical polarity through effects on basolateral laminin assembly. Nat Cell Biol 2001; 3:831-8; PMID: 11533663; http://dx.doi.org/10.1038/ncb0901-831
14. Yu W, Datta A, Leroy P, O’Brien LE, Mak G, Jou TS, Matlin KS, Mostov KE, Zegers MM. Beta1-integrin orients epithelial polarity via Rac1 and laminin. Mol Biol Cell 2005; 16:433-45; PMID:15574881; http://dx.doi.org/10.1091/mbc.E04-05-0435
15. Liu KD, Datta A, Yu W, Brakeman PR, Jou TS, Matthay MA, Mostov KE. Rac1 is required for reorientation of polarity and lumen formation through a PI 3kinase-dependent pathway. Am J Physiol Renal Physiol 2007; 293:F1633-40; PMID:17804488; http://dx.doi.org/10.1152/ajprenal.00053.2007
16. Yu W, Shewan AM, Brakeman P, Eastburn DJ, Datta A, Bryant DM, Fan QW, Weiss WA, Zegers MM, Mostov KE. Involvement of RhoA, ROCK I and myosin II in inverted orientation of epithelial polarity. EMBO Rep 2008; 9:923-9; PMID:18660750; http://dx.doi.org/10.1038/embor.2008.135
17. Mack NA, Porter AP, Whalley HJ, Schwarz JP, Jones RC, Khaja AS, Bjartell A, Anderson KI, Malliri A. beta2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity. Nat Cell Biol 2012; 14:1169-80; PMID:23103911; http://dx.doi.org/10.1038/ncb2608
18. Yagi S, Matsuda M, Kiyokawa E. Suppression of Rac1 activity at the apical membrane of MDCK cells is essential for cyst structure maintenance. EMBO Rep 2012; 13:237-43; PMID:22261715; http://dx.doi.org/10.1038/embor.2011.249
19. Chen X, Macara IG. Par-3 controls tight junction assembly through the Rac exchange factor Tiam1. Nat Cell Biol 2005; 7:262-9; PMID:15723052; http://dx.doi.org/10.1038/ncb1226
20. Horikoshi Y, Suzuki A, Yamanaka T, Sasaki K, Mizuno K, Sawada H, Yonemura S, Ohno S. Interaction between PAR-3 and the aPKC-PAR-6 complex is indispensable for apical domain development of epithelial cells. J Cell Sci 2009; 122:1595-606; PMID: 19401335; http://dx.doi.org/10.1242/jcs.043174
21. Yagi S, Matsuda M, Kiyokawa E. Chimaerin suppresses Rac1 activation at the apical membrane to maintain the cyst structure. PloS One 2012; 7:e52258; PMID:23284959; http://dx.doi.org/10.1371/journal. pone.0052258
22. Georgiou M, Baum B. Polarity proteins and Rho GTPases cooperate to spatially organise epithelial actin-based protrusions. J Cell Sci 2010; 123:1089-1098; PMID:20197404; http://dx.doi.org/10.1242/jcs.060772
23. Gon H, Fumoto K, Ku Y, Matsumoto S, Kikuchi A. Wnt5a signaling promotes apical and basolateral polarization of single epithelial cells. Mol Biol Cell 2013; 24:3764-74; PMID:24088568; http://dx.doi.org/10.1091/mbc.E13-07-0357
24. Martin-Belmonte F, Gassama A, Datta A, Yu W, Rescher U, Gerke V, Mostov K. PTEN-mediated apical segregation of phosphoinositides controls epithelial morphogenesis through Cdc42. Cell 2007; 128:383-397; PMID:17254974; http://dx.doi.org/10.1016/j.cell.2006.11.051
25. Bryant DM, Datta A, Rodriguez-Fraticelli AE, Peranen J, Martin-Belmonte F, Mostov KE. A molecular network for de novo generation of the apical surface and lumen. Nat Cell Biol 2010; 12:1035-45; PMID:20890297; http://dx.doi.org/10.1038/ncb2106
26. Jaffe AB, Kaji N, Durgan J, Hall A. Cdc42 controls spindle orientation to position the apical surface during epithelial morphogenesis. J Cell Biol 2008; 183:625-33; PMID:19001128; http://dx.doi.org/10.1083/jcb.200807121
27. Rodriguez-Fraticelli AE, Vergarajauregui S, Eastburn DJ, Datta A, Alonso MA, Mostov K, Martin-Belmonte F. The Cdc42 GEF Intersectin 2 controls mitotic spindle orientation to form the lumen during epithelial morphogenesis. J Cell Biol 2010; 189:725-738; PMID:20479469; http://dx.doi.org/10.1083/jcb.201002047
28. Qin Y, Meisen WH, Hao Y, Macara IG. Tuba, a Cdc42 GEF, is required for polarized spindle orienta tion during epithelial cyst formation. J Cell Biol 2010; 189:661-9; PMID:20479467; http://dx.doi.org/10.1083/jcb.201002097
29. Lazaro-Dieguez F, Cohen D, Fernandez D, Hodgson L, van Ijzendoorn SC, Musch A. Par1b links lumen polarity with LGN-NuMA positioning for distinct epithelial cell division phenotypes. J Cell Biol 2013; 203:251-64; PMID:24165937; http://dx.doi.org/10.1083/jcb.201303013
30. Kemphues KJ, Priess JR, Morton DG, Cheng NS. Identification of genes required for cytoplasmic locali zation in early C. elegans embryos. Cell 1988; 52:311-20; PMID:3345562; http://dx.doi.org/10.1016/S0092-8674(88)80024-2
31. Etemad-Moghadam B, Guo S, Kemphues KJ. Asym metrically distributed PAR-3 protein contributes to cell polarity and spindle alignment in early C. elegans embryos. Cell 1995; 83:743-52; PMID:8521491; http://dx.doi.org/10.1016/0092-8674(95)90187-6
32. Grill SW, Gonczy P, Stelzer EH, Hyman AA. Polarity controls forces governing asymmetric spindle positioning in the Caenorhabditis elegans embryo. Nature 2001; 409:630-3; PMID:11214323; http://dx.doi.org/10.1038/35054572
33. Hung TJ, Kemphues KJ. PAR-6 is a conserved PDZ domain-containing protein that colocalizes with PAR 3 in Caenorhabditis elegans embryos. Development 1999; 126:127-35; PMID:9834192
34. Gotta M, Abraham MC, Ahringer J. CDC-42 controls early cell polarity and spindle orientation in C. elegans. Curr Biol: CB 2001; 11:482-8; PMID:11412997; http://dx.doi.org/10.1016/S0960-9822(01)00142-7
35. Perez P, Rincon SA. Rho GTPases: regulation of cell polarity and growth in yeasts. The Biochemical jour nal 2010; 426:243-53; PMID:20175747; http://dx.doi.org/10.1042/BJ20091823
36. Joberty G, Petersen C, Gao L, Macara IG. The cell polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nat Cell Biol 2000; 2:531-9; PMID:10934474; http://dx.doi.org/10.1038/35019573
37. Johansson A, Driessens M, Aspenstrom P. The mam malian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1. J Cell Sci 2000; 113 (Part 18):3267-75; PMID:10954424
38. Lin D, Edwards AS, Fawcett JP, Mbamalu G, Scott JD, Pawson T. A mammalian PAR-3-PAR-6 complex implicated in Cdc42Rac1 and aPKC signalling and cell polarity. Nat Cell Biol 2000; 2:540-7; PMID:10934475; http://dx.doi.org/10.1038/35019592
39. Qiu RG, Abo A, Steven Martin G. A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCzeta signaling and cell transformation. Curr Biol: CB 2000; 10:697-707; PMID:10873802; http://dx.doi.org/10.1016/S09609822(00)00535-2
40. Hutterer A, Betschinger J, Petronczki M, Knoblich JA. Sequential roles of Cdc42, Par-6, aPKC, and Lgl in the establishment of epithelial polarity during Drosophila embryogenesis. Dev Cell 2004; 6:845-54; PMID:15177032; http://dx.doi.org/10.1016/j.devcel.2004.05.003
41. Georgiou M, Marinari E, Burden J, Baum B. Cdc42, Par6, and aPKC regulate Arp23-mediated endocytosis to control local adherens junction stability. Curr Biol: CB 2008; 18:1631-8; PMID:18976918; http://dx.doi.org/10.1016/j.cub.2008.09.029
42. Atwood SX, Chabu C, Penkert RR, Doe CQ, Pre hoda KE. Cdc42 acts downstream of Bazooka to regu late neuroblast polarity through Par-6 aPKC. J Cell Sci 2007; 120:3200-6; PMID:17726059; http://dx.doi.org/10.1242/jcs.014902
43. Yamanaka T, Horikoshi Y, Suzuki A, Sugiyama Y, Kitamura K, Maniwa R, Nagai Y, Yamashita A, Hirose T, Ishikawa H, et al. PAR-6 regulates aPKC activity in a novel way and mediates cell-cell contactinduced formation of the epithelial junctional complex. Genes Cells: Dev Mol Cell Mech 2001; 6:721-731; PMID:11532031; http://dx.doi.org/10.1046/j.1365-2443.2001.00453.x
44. Garrard SM, Capaldo CT, Gao L, Rosen MK, Macara IG, Tomchick DR. Structure of Cdc42 in a complex with the GTPase-binding domain of the cell polarity protein, Par6. EMBO J 2003; 22:1125-33; PMID:12606577; http://dx.doi.org/10.1093/emboj/cdg110
45. Hurd TW, Gao L, Roh MH, Macara IG, Margolis B. Direct interaction of two polarity complexes imply cated in epithelial tight junction assembly. Nat Cell Biol 2003; 5:137-42; PMID:12545177; http://dx.doi.org/10.1038/ncb923
46. Penkert RR, DiVittorio HM, Prehoda KE. Internal recognition through PDZ domain plasticity in the Par-6-Pals1 complex. Nat Struct Mol Biol 2004; 11:1122-7; PMID:15475968; http://dx.doi.org/10.1038/nsmb839
47. Walther RF, Pichaud F. Crumbs DaPKC-dependent apical exclusion of Bazooka promotes photoreceptor polarity remodeling. Curr Biol: CB 2010; 20:1065-1074; PMID:20493700; http://dx.doi.org/10.1016/j.cub.2010.04.049
48. Morais-de-Sa E, Mirouse V, St Johnston D. aPKC phosphorylation of Bazooka defines the apicallateral border in Drosophila epithelial cells. Cell 2010; 141:509-23; PMID:20434988; http://dx.doi.org/10.1016/j.cell.2010.02.040
49. Schluter MA, Pfarr CS, Pieczynski J, Whiteman EL, Hurd TW, Fan S, Liu CJ, Margolis B. Trafficking of Crumbs3 during cytokinesis is crucial for lumen formation. Mol Biol Cell 2009; 20:4652-63; PMID:19776356; http://dx.doi.org/10.1091/mbc. E09-02-0137
50. Zihni C, Munro PM, Elbediwy A, Keep NH, Terry SJ, Harris J, Balda MS, Matter K. Dbl3 drives Cdc42 signaling at the apical margin to regulate junction position and apical differentiation. J Cell Biol 2014; 204:111-27; PMID:24379416; http://dx.doi.org/10.1083/jcb.201304064
51. McKinley RF, Yu CG, Harris TJ. Assembly of Bazooka polarity landmarks through a multifaceted membrane-association mechanism. J Cell Sci 2012; 125:1177-90; PMID:22303000; http://dx.doi.org/10.1242/jcs.091884
52. Itoh M, Sasaki H, Furuse M, Ozaki H, Kita T, Tsu kita S. Junctional adhesion molecule (JAM) binds to PAR-3: a possible mechanism for the recruitment of PAR-3 to tight junctions. J Cell Biol 2001; 154:491-497; PMID:11489913; http://dx.doi.org/10.1083/jcb.200103047
53. Capaldo CT, Macara IG. Depletion of E-cadherin disrupts establishment but not maintenance of cell junctions in Madin-Darby canine kidney epithelial cells. Mol Biol Cell 2007; 18:189-200; PMID: 17093058; http://dx.doi.org/10.1091/mbc.E06-05-0471
54. Vasioukhin V, Bauer C, Yin M, Fuchs E. Directed actin polymerization is the driving force for epithelial cell-cell adhesion. Cell 2000; 100:209-19; PMID:10660044; http://dx.doi.org/10.1016/S0092 8674(00)81559-7
55. Ehrlich JS, Hansen MD, Nelson WJ. Spatio-temporal regulation of Rac1 localization and lamellipodia dynamics during epithelial cell-cell adhesion. Dev Cell 2002; 3:259-70; PMID:12194856; http://dx.doi.org/10.1016/S1534-5807(02)00216-2
56. Kovacs EM, Goodwin M, Ali RG, Paterson AD, Yap AS. Cadherin-directed actin assembly: E-cadherin physically associates with the Arp23 complex to direct actin assembly in nascent adhesive contacts. Curr Biol 2002; 12:379-82; PMID:11882288; http://dx.doi.org/10.1016/S0960-9822(02)00661-9
57. Lambert M, Choquet D, Mege RM. Dynamics of ligand-induced, Rac1-dependent anchoring of cadher ins to the actin cytoskeleton. J Cell Biol 2002; 157:469-79; PMID:11970959; http://dx.doi.org/10.1083/jcb.200107104
58. Gavard J, Lambert M, Grosheva I, Marthiens V, Irinopoulou T, Riou JF, Bershadsky A, Mege RM. Lamellipodium extension and cadherin adhesion: two cell responses to cadherin activation relying on distinct signalling pathways. J Cell Sci 2004; 117:257-70; PMID:14657280; http://dx.doi.org/10.1242/jcs.00857
59. Hoshino T, Shimizu K, Honda T, Kawakatsu T, Fukuyama T, Nakamura T, Matsuda M, Takai Y. A novel role of nectins in inhibition of the E-cadherininduced activation of Rac and formation of cell-cell adherens junctions. Mol Biol Cell 2004; 15:1077-88; PMID:14699074; http://dx.doi.org/10.1091/mbc. E03-05-0321
60. Adams CL, Chen YT, Smith SJ, Nelson WJ. Mecha nisms of epithelial cell-cell adhesion and cell compact tion revealed by high-resolution tracking of Ecadherin-green fluorescent protein. J Cell Biol 1998; 142:1105-19; PMID:9722621; http://dx.doi.org/10.1083/jcb.142.4.1105
61. Krendel MF, Bonder EM. Analysis of actin filament bundle dynamics during contact formation in live epi thelial cells. Cell Motil Cytoskel 1999; 43:296-309; PMID:10423271; http://dx.doi.org/10.1002/(SICI) 1097-0169(1999)43:4%3c296::AID-CM3%3e3.0.CO;2-U
62. Kobielak A, Pasolli HA, Fuchs E. Mammalian for min-1 participates in adherens junctions and polymerization of linear actin cables. Nat Cell Biol 2004; 6:21-30; PMID:14647292; http://dx.doi.org/; http://dx.doi.org/10.1038/ncb1075
63. Wallace SW, Durgan J, Jin D, Hall A. Cdc42 regu lates apical junction formation in human bronchial epithelial cells through PAK4 and Par6B. Mol Biol Cell 2010; 21:2996-3006; PMID:20631255; http://dx.doi.org/10.1091/mbc.E10-05-0429
64. Kuroda S, Fukata M, Fujii K, Nakamura T, Izawa I, Kaibuchi K. Regulation of cell-cell adhesion of MDCK cells by Cdc42 and Rac1 small GTPases. Biochem Biophys Res Commun 1997; 240:430-5; PMID:9388496; http://dx.doi.org/10.1006/bbrc.1997.7675
65. Takaishi K, Sasaki T, Kameyama T, Tsukita S, Takai Y. Translocation of activated Rho from the cytoplasm to membrane ruffling area, cell-cell adhesion sites and cleavage furrows. Oncogene 1995; 11:39-48; PMID:7624130
66. Takaishi K, Sasaki T, Kotani H, Nishioka H, Takai Y. Regulation of cell-cell adhesion by rac and rho small G proteins in MDCK cells. J Cell Biol 1997; 139:1047-59; PMID:9362522; http://dx.doi.org/10.1083/jcb.139.4.1047
67. Eaton S, Auvinen P, Luo L, Jan YN, Simons K. CDC42 and Rac1 control different actin-dependent processes in the Drosophila wing disc epithelium. J Cell Biol 1995; 131:151-64; PMID:7559772; http://dx.doi.org/10.1083/jcb.131.1.151
68. Braga VM, Machesky LM, Hall A, Hotchin NA. The small GTPases Rho and Rac are required for the estab lishment of cadherin-dependent cell-cell contacts. J Cell Biol 1997; 137:1421-31; PMID:9182672; http://dx.doi.org/10.1083/jcb.137.6.1421
69. Hordijk PL, ten Klooster JP, van der Kammen RA, Michiels F, Oomen LC, Collard JG. Inhibition of invasion of epithelial cells by Tiam1-Rac signaling. Science 1997; 278:1464-6; PMID:9367959; http://dx.doi.org/10.1126/science.278.5342.1464
70. Kovacs EM, Ali RG, McCormack AJ, Yap AS. E-cad herin homophilic ligation directly signals through Rac and phosphatidylinositol 3-kinase to regulate adhesive contacts. J Biol Chem 2002; 277:6708-18; PMID: 11744701; http://dx.doi.org/10.1074/jbc.M109640200
71. Kawakatsu T, Shimizu K, Honda T, Fukuhara T, Hoshino T, Takai Y. Trans-interactions of nectins induce formation of filopodia and Lamellipodia through the respective activation of Cdc42 and Rac small G proteins. J Biol Chem 2002; 277:50749-55; PMID:12379640; http://dx.doi.org/10.1074/jbc.M209846200
72. Nakagawa M, Fukata M, Yamaga M, Itoh N, Kaibu chi K. Recruitment and activation of Rac1 by the for mation of E-cadherin-mediated cell-cell adhesion sites. J Cell Sci 2001; 114:1829-38; PMID:11329369
73. Noren NK, Niessen CM, Gumbiner BM, Burridge K. Cadherin engagement regulates Rho family GTPases. J Biol Chem 2001; 276:33305-33308; PMID:11457821; http://dx.doi.org/10.1074/jbc.C100306200
74. Kitt KN, Nelson WJ. Rapid suppression of activatedRac1 by cadherins and nectins during de novo cell-cell adhesion. PloS One 2011; 6:e17841; PMID: 21412440; http://dx.doi.org/10.1371/journal.pone.0017841
75. Yamada S, Nelson WJ. Localized zones of Rho and Rac activities drive initiation and expansion of epithelial cell-cell adhesion. J Cell Biol 2007; 178: 517-527; PMID:17646397; http://dx.doi.org/10.1083/jcb.200701058
76. McNeill H, Ryan TA, Smith SJ, Nelson WJ. Spatial and temporal dissection of immediate and early events following cadherin-mediated epithelial cell adhesion. J Cell Biol 1993; 120:1217-1226; PMID:8436592; http://dx.doi.org/10.1083/jcb.120.5.1217
77. Adams CL, Nelson WJ, Smith SJ. Quantitative analy sis of cadherin-catenin-actin reorganization during development of cell-cell adhesion. J Cell Biol 1996; 135:1899-911; PMID:8991100
78. Adams CL, Nelson WJ. Cytomechanics of cadherin mediated cell-cell adhesion. Curr Opin Cell Biol 1998; 10:572-7; PMID:9818166
79. Krendel M, Gloushankova NA, Bonder EM, Feder HH, Vasiliev JM, Gelfand IM. Myosin-dependent contractile activity of the actin cytoskeleton modulates the spatial organization of cell-cell contacts in cultured epitheliocytes. Proc Nat Acad Sci U S A 1999; 96:9666-70; PMID:10449751
80. Ivanov AI, McCall IC, Parkos CA, Nusrat A. Role for actin filament turnover and a myosin II motor in cyto skeleton-driven disassembly of the epithelial apical junctional complex. Mol Biol Cell 2004; 15:2639-51; PMID:15047870
81. Ivanov AI, Hunt D, Utech M, Nusrat A, Parkos CA. Differential roles for actin polymerization and a myo sin II motor in assembly of the epithelial apical junctional complex. Mol Biol Cell 2005; 16:2636-50; PMID:15800060
82. Shewan AM, Maddugoda M, Kraemer A, Stehbens SJ, Verma S, Kovacs EM, Yap AS. Myosin 2 is a key Rho kinase target necessary for the local concentration of E-cadherin at cell-cell contacts. Mol Biol Cell 2005; 16:4531-42; PMID:16030252
83. Raich WB, Agbunag C, Hardin J. Rapid epithelial sheet sealing in the Caenorhabditis elegans embryo requires cadherin-dependent filopodial priming. Curr Biol: CB 1999; 9:1139-46; PMID:10531027
84. Jacinto A, Wood W, Balayo T, Turmaine M, Martinez Arias A, Martin P. Dynamic actin-based epithelial adhesion and cell matching during Drosophila dorsal closure. Curr Biol: CB 2000; 10:1420-6; PMID:11102803
85. Jacinto A, Woolner S, Martin P. Dynamic analysis of dorsal closure in Drosophila: from genetics to cell biology. Dev Cell 2002; 3:9-19; PMID:12110163
86. Brock J, Midwinter K, Lewis J, Martin P. Healing of incisional wounds in the embryonic chick wing bud: characterization of the actin purse-string and demonstration of a requirement for Rho activation. J Cell Biol 1996; 135:1097-107; PMID:8922389
87. Elbediwy A, Zihni C, Terry SJ, Clark P, Matter K, Balda MS. Epithelial junction formation requires confinement of Cdc42 activity by a novel SH3BP1 complex. J Cell Biol 2012; 198:677-93; PMID:22891260
88. Kim SH, Li Z, Sacks DB. E-cadherin-mediated cell cell attachment activates Cdc42. J Biol Chem 2000; 275:36999-7005; PMID:10950951
89. Erasmus J, Aresta S, Nola S, Caron E, Braga VM. Newly formed E-cadherin contacts do not activate Cdc42 or induce filopodia protrusion in human keratinocytes. Biol Cell Under Auspices Eur Cell Biol Organ 2010; 102:13-24
90. Barcellos KS, Bigarella CL, Wagner MV, Vieira KP, Lazarini M, Langford PR, Machado-Neto JA, Call SG, Staley DM, Chung JY, et al. ARHGAP21 protein, a new partner of alpha-tubulin involved in cellcell adhesion formation and essential for epithelialmesenchymal transition. J Biol Chem 2013; 288:2179-89; PMID:23235160
91. Du D, Pedersen E, Wang Z, Karlsson R, Chen Z, Wu X, Brakebusch C. Cdc42 is crucial for the maturation of primordial cell junctions in keratinocytes independent of Rac1. Exp Cell Res 2009; 315:1480-9; PMID:19100259
92. Malliri A, van Es S, Huveneers S, Collard JG. The Rac exchange factor Tiam1 is required for the establish ment and maintenance of cadherin-based adhesions. J Biol Chem 2004; 279:30092-8; PMID:15138270; http://dx.doi.org/10.1074/jbc.M401192200
93. Woodcock SA, Rooney C, Liontos M, Connolly Y, Zoumpourlis V, Whetton AD, Gorgoulis VG, Malliri A. SRC-induced disassembly of adherens junctions requires localized phosphorylation and degradation of the rac activator tiam1. Mol Cell 2009; 33:639-53; PMID:19285946; http://dx.doi.org/10.1016/j.molcel.2009.02.012
94. Kuroda S, Fukata M, Nakagawa M, Fujii K, Naka mura T, Ookubo T, Izawa I, Nagase T, Nomura N, Tani H, et al. Role of IQGAP1, a target of the small GTPases Cdc42 and Rac1, in regulation of E-cadherinmediated cell-cell adhesion. Science 1998; 281:832-5; PMID:9694656; http://dx.doi.org/10.1126/science.281.5378.832
95. Fukata M, Kuroda S, Nakagawa M, Kawajiri A, Itoh N, Shoji I, Matsuura Y, Yonehara S, Fujisawa H, Kikuchi A, et al. Cdc42 and Rac1 regulate the interaction of IQGAP1 with beta-catenin. J Biol Chem 1999; 274:26044-50; PMID:10473551; http://dx.doi.org/10.1074/jbc.274.37.26044
96. Nola S, Daigaku R, Smolarczyk K, Carstens M, Mar tin-Martin B, Longmore G, Bailly M, Braga VM. Ajuba is required for Rac activation and maintenance of E-cadherin adhesion. J Cell Biol 2011; 195:855-871; PMID:22105346; http://dx.doi.org/10.1083/jcb.201107162
97. Ratheesh A, Gomez GA, Priya R, Verma S, Kovacs EM, Jiang K, Brown NH, Akhmanova A, Stehbens SJ, Yap AS. Centralspindlin and alpha-catenin regulate Rho signalling at the epithelial zonula adherens. Nat Cell Biol 2012; 14:818-28; PMID:22750944; http://dx.doi.org/10.1038/ncb2532
98. Su KC, Takaki T, Petronczki M. Targeting of the RhoGEF Ect2 to the equatorial membrane controls cleavage furrow formation during cytokinesis. Dev Cell 2011; 21:1104-15; PMID:22172673; http://dx.doi.org/10.1016/j.devcel.2011.11.003
99. Ngok SP, Geyer R, Kourtidis A, Mitin N, Feathers R, Der C, Anastasiadis PZ. TEM4 is a junctional Rho GEF required for cell-cell adhesion, monolayer integrity and barrier function. J Cell Sci 2013; 126:3271-3277; PMID:23729734; http://dx.doi.org/10.1242/jcs.123869SmallGTPases
100. Sahai E, Marshall CJ. ROCK and Dia have opposingffects on adherens junctions downstream of Rho. Nat Cell Biol 2002; 4:408-15; PMID:11992112; http://dx.doi.org/10.1038/ncb796
101. Smutny M, Cox HL, Leerberg JM, Kovacs EM, Conti MA, Ferguson C, Hamilton NA, Parton RG, Adel stein RS, Yap AS. Myosin II isoforms identify distinct functional modules that support integrity of the epithelial zonula adherens. Nat Cell Biol 2010; 12:696-702; PMID:20543839; http://dx.doi.org/10.1038/ncb2072
102. Katayama K, Melendez J, Baumann JM, Leslie JR, Chauhan BK, Nemkul N, Lang RA, Kuan CY, Zheng Y, Yoshida Y. Loss of RhoA in neural progenitor cells causes the disruption of adherens junctions and hyperproliferation. Proc Nat Acad Sci U S A 2011; 108:7607-12; PMID:21502507; http://dx.doi.org/10.1073/pnas.1101347108
103. Bonacci TM, Hirsch DS, Shen Y, Dokmanovic M, Wu WJ. Small GTPase Rho regulates R-cadherin through Dia1profilin-1. Cell Signalling 2012; 24:2102-10; PMID:22820501; http://dx.doi.org/10.1016/j.cellsig.2012.07.015
104. Herzog D, Loetscher P, van Hengel J, Knusel S, Brakebusch C, Taylor V, Suter U, Relvas JB. The small GTPase RhoA is required to maintain spinal cord neuroepithelium organization and the neural stem cell pool. J Neurosci: Off J Soci Neurosci 2011; 31:5120-30; PMID:21451048; http://dx.doi.org/10.1523/JNEUROSCI.4807-10.2011
105. Bertet C, Sulak L, Lecuit T. Myosin-dependent junction remodelling controls planar cell intercalation and axis elon gation. Nature 2004; 429:667-71; PMID:15190355; http://dx.doi.org/10.1038/nature02590
106. Dawes-Hoang RE, Parmar KM, Christiansen AE, Phelps CB, Brand AH, Wieschaus EF. Folded gastrulation, cell shape change and the control of myosin localization. Development 2005; 132:4165-78; PMID:16123312; http://dx.doi.org/10.1242/dev.01938
107. Blankenship JT, Backovic ST, Sanny JS, Weitz O, Zallen JA. Multicellular rosette formation links planar cell polarity to tissue morphogenesis. Dev Cell 2006; 11:459-70; PMID:17011486; http://dx.doi.org/10.1016/j.devcel.2006.09.007
108. Abraham S, Yeo M, Montero-Balaguer M, Paterson H, Dejana E, Marshall CJ, Mavria G. VE-Cadherin mediated cell-cell interaction suppresses sprouting via signaling to MLC2 phosphorylation. Curr Biol 2009; 19:668-74; PMID:19345098; http://dx.doi.org/10.1016/j.cub.2009.02.057
109. Martin AC, Kaschube M, Wieschaus EF. Pulsed con tractions of an actin-myosin network drive apical con striction. Nature 2009; 457:495-9; PMID:19029882; http://dx.doi.org/10.1038/nature07522
110. Liu Z, Tan JL, Cohen DM, Yang MT, Sniadecki NJ, Ruiz SA, Nelson CM, Chen CS. Mechanical tugging force regulates the size of cell-cell junctions. Proc Natl Acad Sci U S A 2010; 107:9944-9; PMID:20463286; http://dx.doi.org/10.1073/pnas.0914547107
111. Fujita Y, Krause G, Scheffner M, Zechner D, Leddy HE, Behrens J, Sommer T, Birchmeier W. Hakai, a c Cbllike protein, ubiquitinates and induces endocytosis of the E-cadherin complex. Nat Cell Biol 2002; 4:222-31; PMID:11836526; http://dx.doi.org/10.1038/ncb758
112. Pilot F, Philippe JM, Lemmers C, Lecuit T. Spatial control of actin organization at adherens junctions by a synaptotagmin-like protein Btsz. Nature 2006; 442:580-4; PMID:16862128; http://dx.doi.org/10.1038/nature04935
113. Cavey M, Rauzi M, Lenne PF, Lecuit T. A two-tiered mechanism for stabilization and immobilization of E cadherin. Nature 2008; 453:751-6; PMID:18480755; http://dx.doi.org/10.1038/nature06953
114. de Beco S, Gueudry C, Amblard F, Coscoy S. Endo cytosis is required for Ecadherin redistribution at mature adherens junctions. Proc Natl Acad Sci U S A 2009; 106:7010-5; PMID:19372377; http://dx.doi.org/10.1073/pnas.0811253106
115. Le TL, Yap AS, Stow JL. Recycling of E-cadherin: a potential mechanism for regulating cadherin dynam ics. J Cell Biol 1999; 146:219-32; PMID:10402472; http://dx.doi.org/10.1083/jcb.146.1.219
116. Langevin J, Morgan MJ, Sibarita JB, Aresta S, Murthy M, Schwarz T, Camonis J, Bellaiche Y. Drosophila exocyst components Sec5, Sec6, and Sec15 regulate DE-Cadherin trafficking from recycling endosomes to the plasma membrane. Dev Cell 2005; 9:355-76; PMID:16224820; http://dx.doi.org/10.1016/j.devcel. 2005.07.013
117. Leibfried A, Fricke R, Morgan MJ, Bogdan S, Bel laiche Y. Drosophila Cip4 and WASp define a branch of the Cdc42-Par6-aPKC pathway regulating E-cadherin endocytosis. Curr Biol: CB 2008; 18:1639-48; PMID:18976911; http://dx.doi.org/10.1016/j.cub.2008.09.063
118. Harris KP, Tepass U. Cdc42 and Par proteins stabilize dynamic adherens junctions in the Drosophila neur ectoderm through regulation of apical endocytosis. J Cell Biol 2008; 183:1129-43; PMID:19064670; http://dx.doi.org/10.1083/jcb.200807020
119. Warner SJ, Longmore GD. Cdc42 antagonizes Rho1 activity at adherens junctions to limit epithelial cell apical tension. J Cell Biol 2009; 187:119-33; PMID: 19805632; http://dx.doi.org/10.1083/jcb.200906047
120. Warner SJ, Longmore GD. Distinct functions for Rho1 in maintaining adherens junctions and apical tension in remodeling epithelia. J Cell Biol 2009; 185:1111-25; PMID:19506041; http://dx.doi.org/10.1083/jcb.200901029
121. Yamada S, Pokutta S, Drees F, Weis WI, Nelson WJ. Deconstructing the cadherin-catenin-actin complex. Cell 2005; 123:889-901; PMID:16325582; http://dx.doi.org/10.1016/j.cell.2005.09.020
122. Miyoshi J, Takai Y. Nectin and nectin-like molecules: biology and pathology. Am J Nephrol 2007; 27:590-604; PMID:17823505; http://dx.doi.org/10.1159/000108103
123. Furman C, Sieminski AL, Kwiatkowski AV, Rubinson DA, Vasile E, Bronson RT, Fassler R, Gertler FB. EnaVASP is required for endothelial barrier function in vivo. J Cell Biol 2007; 179:761-75; PMID: 17998398; http://dx.doi.org/10.1083/jcb.200705002
124. Goode BL, Eck MJ. Mechanism and function of for mins in the control of actin assembly. Ann Rev Biochem 2007; 76:593-627; PMID:17373907; http://dx.doi.org/10.1146/annurev.biochem.75.103004.142647
125. Yano T, Yamazaki Y, Adachi M, Okawa K, Fort P, Uji M, Tsukita S. Tara up-regulates E-cadherin transcription by binding to the Trio RhoGEF and inhibiting Rac signaling. J Cell Biol 2011; 193:319-32; PMID: 21482718; http://dx.doi.org/10.1083/jcb.201009100
126. Hage B, Meinel K, Baum I, Giehl K, Menke A. Rac1 activation inhibits E-cadherin-mediated adherens junctions via binding to IQGAP1 in pancreatic carcinoma cells. Cell Commun Signaling: CCS 2009; 7:23; PMID:19737400; http://dx.doi.org/10.1186/1478-811X-7-23
127. Lozano E, Frasa MA, Szolarczyk K, Knaus UG, Braga VM. PAK is required for the disruption of E cadherin adhesion by the small GTPase Rac. J Cell Sci 2008; 121:933-8; PMID:18319303; http://dx.doi.org/10.1242/jcs.016121
128. Braga VM, Betson M, Li X, Lamarche-Vane N. Acti vation of the small GTPase Rac is sufficient to disrupt cadherindependent cell-cell adhesion in normal human keratinocytes. Mol Biol Cell 2000; 11:3703 21; PMID:11071901; http://dx.doi.org/10.1091/mbc.11.11.3703
129. Akhtar N, Hotchin NA. RAC1 regulates adherens junctions through endocytosis of E-cadherin. Mol Biol Cell 2001; 12:847-62; PMID:11294891; http://dx.doi.org/10.1091/mbc.12.4.847
130. Fischer RS, Quinlan MP. Identification of a novel mechanism of regulation of the adherens junction by 14 E1A, Rac1, and cortical actin filaments that contributes to tumor progression. Cell Growth Differ: Mol Biol J Am Assoc Cancer Res 1998; 9:905-18
131. Quinlan MP. Rac regulates the stability of the adhe rens junction and its components, thus affecting epi thelial cell differentiation and transformation. Oncogene 1999; 18:6434-42; PMID:10597245; http://dx.doi.org/10.1038/sj.onc.1203026
132. Kawasaki Y, Sato R, Akiyama T. Mutated APC and Asef are involved in the migration of colorectal tumour cells. Nat Cell Biol 2003; 5:211-5; PMID:12598901; http://dx.doi.org/10.1038/ncb937 . Potempa S, Ridley AJ. Activation of both MAP kinase and phosphatidylinositide 3-kinase by Ras is required for hepatocyte growth factorscatter factor-induced adherens junction disassembly. Mol Biol Cell 1998; 9:2185-200; PMID:9693375; http://dx.doi.org/10.1091/mbc.9.8.2185
133. Shintani Y, Wheelock MJ, Johnson KR. Phosphoino sitide-3 kinase-Rac1-c-Jun NH2-terminal kinase sig naling mediates collagen I-induced cell scattering and up-regulation of N-cadherin expression in mouse mammary epithelial cells. Mol Biol Cell 2006; 17:2963-75; PMID:16624865; http://dx.doi.org/10.1091/mbc.E05-12-1123
134. Yagi R, Waguri S, Sumikawa Y, Nada S, Oneyama C, Itami S, Schmedt C, Uchiyama Y, Okada M. C-ter minal Src kinase controls development and maintenance of mouse squamous epithelia. EMBO J 2007; 26:1234-44; PMID:17304209; http://dx.doi.org/10.1038/sj.emboj.7601595
135. Holeiter G, Bischoff A, Braun AC, Huck B, Erlmann P, Schmid S, Herr R, Brummer T, Olayioye MA. The RhoGAP protein Deleted in Liver Cancer 3 (DLC3) is essential for adherens junctions integrity. Oncogenesis 2012; 1:e13; PMID:23552697; http://dx.doi.org/10.1038/oncsis.2012.13
136. Hopkins AM, Walsh SV, Verkade P, Boquet P, Nus rat A. Constitutive activation of Rho proteins by CNF-1 influences tight junction structure and epithelial barrier function. J Cell Sci 2003; 116:725-42; PMID:12538773; http://dx.doi.org/10.1242/jcs.00300
137. Bruewer M, Hopkins AM, Hobert ME, Nusrat A, Madara JL. RhoA, Rac1, and Cdc42 exert distinct effects on epithelial barrier via selective structural and biochemical modulation of junctional proteins and Factin. Am J Physiol Cell Physiol 2004; 287:C327-35; PMID:15044152; http://dx.doi.org/10.1152/ajpcell.00087.2004
138. Jou TS, Schneeberger EE, Nelson WJ. Structural and functional regulation of tight junctions by RhoA and Rac1 small GTPases. J Cell Biol 1998; 142:101-15; PMID:9660866; http://dx.doi.org/10.1083/jcb.142. 1.101
139. Rojas R, Ruiz WG, Leung SM, Jou TS, Apodaca G. Cdc42-dependent modulation of tight junctions and membrane protein traffic in polarized Madin-Darby canine kidney cells. Mol Biol Cell 2001; 12:2257-74; PMID:11514615; http://dx.doi.org/10.1091/mbc.12.8.2257
140. Nusrat A, Giry M, Turner JR, Colgan SP, Parkos CA, Carnes D, Lemichez E, Boquet P, Madara JL. Rho protein regulates tight junctions and perijunctional actin organization in polarized epithelia. Proc Nat Acad Sci U S A 1995; 92:10629-33; PMID:7479854; http://dx.doi.org/10.1073/pnas.92.23.10629
141. Terry SJ, Zihni C, Elbediwy A, Vitiello E, Leefa Chong San IV, Balda MS, Matter K. Spatially restricted activation of RhoA signalling at epithelial junctions by p114RhoGEF drives junction formation and morphogenesis. Nat Cell Biol 2011; 13:159-66; PMID:21258369; http://dx.doi.org/10.1038/ncb2156
142. Itoh M, Tsukita S, Yamazaki Y, Sugimoto H. Rho GTP exchange factor ARHGEF11 regulates the integrity of epithelial junctions by connecting ZO-1 and RhoA-myosin II signaling. Proc Nat Acad Sci U S A 2012; 109:9905-10; PMID:22665792; http://dx.doi.org/10.1073/pnas.1115063109
143. Herder C, Swiercz JM, Muller C, Peravali R, Quiring R, Offermanns S, Wittbrodt J, Loosli F. ArhGEF18 regulates RhoA-Rock2 signaling to maintain neuroepithelial apico-basal polarity and proliferation. Development 2013; 140:2787-97; PMID:23698346; http://dx.doi.org/10.1242/dev.096487
144. Nakajima H, Tanoue T. Lulu2 regulates the circum ferential actomyosin tensile system in epithelial cells through p114RhoGEF. J Cell Biol 2011; 195:245-61; PMID:22006950; http://dx.doi.org/10.1083/jcb.201104118
145. Xu X, Jin D, Durgan J, Hall A. LKB1 controls human bronchial epithelial morphogenesis through p114RhoGEF-dependent RhoA activation. Mol Cell Biol 2013; 33:2671-82; PMID:23648482; http://dx.doi.org/10.1128/MCB.00154-13
146. Terry S, Nie M, Matter K, Balda MS. Rho signaling and tight junction functions. Physiol (Bethesda) 2010; 25:16-26; PMID:20134025; http://dx.doi.org/10.1152/physiol.00034.2009
147. Hasegawa H, Fujita H, Katoh H, Aoki J, Nakamura K, Ichikawa A, Negishi M. Opposite regulation of transepithelial electrical resistance and paracellular permeability by Rho in Madin-Darby canine kidney cells. J Biol Chem 1999; 274:20982-8; PMID: 10409646; http://dx.doi.org/10.1074/jbc.274.30.20982
148. Mertens AE, Rygiel TP, Olivo C, van der Kammen R, Collard JG. The Rac activator Tiam1 controls tight junction biogenesis in keratinocytes through binding to and activation of the Par polarity complex. J Cell Biol 2005; 170:1029-37; PMID:16186252; http://dx.doi.org/10.1083/jcb.200502129
149. Guillemot L, Paschoud S, Jond L, Foglia A, Citi S. Paracingulin regulates the activity of Rac1 and RhoA GTPases by recruiting Tiam1 and GEF-H1 to epithelial junctions. Mol Biol Cell 2008; 19:4442-53; PMID:18653465; http://dx.doi.org/10.1091/mbc. E08-06-0558
150. El-Hashash AH, Turcatel G, Varma S, Berika M, Al Alam D, Warburton D. Eya1 protein phosphatase regulates tight junction formation in lung distal epithelium. J Cell Sci 2012; 125:4036-48; PMID: 22685326; http://dx.doi.org/10.1242/jcs.102848
151. Otani T, Ichii T, Aono S, Takeichi M. Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells. J Cell Biol 2006; 175:135-46; PMID: 17015620; http://dx.doi.org/10.1083/jcb.200605012
152. Togawa A, Sfakianos J, Ishibe S, Suzuki S, Fujigaki Y, Kitagawa M, Mellman I, Cantley LG. Hepatocyte Growth Factor stimulated cell scattering requires ERK and Cdc42-dependent tight junction disassembly. Biochem Biophys Res Commun 2010; 400:271-7; PMID:20728428; http://dx.doi.org/10.1016/j.bbrc.2010.08.060
153. Aijaz S, D’Atri F, Citi S, Balda MS, Matter K. Bind ing of GEF-H1 to the tight junction-associated adap tor cingulin results in inhibition of Rho signaling and G1S phase transition. Dev Cell 2005; 8:777-86; PMID:15866167; http://dx.doi.org/10.1016/j.devcel.2005.03.003
154. Samarin SN, Ivanov AI, Flatau G, Parkos CA, Nusrat A. RhoRho-associated kinase-II signaling mediates disassembly of epithelial apical junctions. Mol Biol Cell 2007; 18:3429-39; PMID:17596509; http://dx.doi.org/10.1091/mbc.E07-04-0315
155. Benais-Pont G, Punn A, Flores-Maldonado C, Eckert J, Raposo G, Fleming TP, Cereijido M, Balda MS, Matter K. Identification of a tight junction-associated guanine nucleotide exchange factor that activates Rho and regulates paracellular permeability. J Cell Biol 2003; 160:729-40; PMID:12604587; http://dx.doi.org/10.1083/jcb.200211047
156. Nie M, Aijaz S, Leefa Chong San IV, Balda MS, Mat ter K. The Y-box factor ZONABDbpA associates with GEF-H1Lfc and mediates Rho-stimulated transcription. EMBO Rep 2009; 10:1125-31; PMID: 19730435; http://dx.doi.org/10.1038/embor.2009.182Volume5Issue2
157. Coleman ML, Marshall CJ, Olson MF. RAS and RHO GTPases in G1-phase cell-cycle regulation. Nat Rev Mol Cell Biol 2004; 5:355-66; PMID:15122349; http://dx.doi.org/10.1038/nrm1365
158. Wells CD, Fawcett JP, Traweger A, Yamanaka Y, Goudreault M, Elder K, Kulkarni S, Gish G, Virag C, Lim C, et al. A Rich1Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells. Cell 2006; 125:535-48; PMID:16678097; http://dx.doi.org/10.1016/j.cell.2006.02.045
159. Yang L, Wang L, Zheng Y. Gene targeting of Cdc42 and Cdc42GAP affirms the critical involvement of Cdc42 in filopodia induction, directed migration, and proliferation in primary mouse embryonic fibroblasts. Mol Biol Cell 2006; 17:4675-85; PMID:16914516; http://dx.doi.org/10.1091/mbc.E06-05-0466
160. Irvine KD, Wieschaus E. Cell intercalation during Drosophila germband extension and its regulation by pair-rule segmentation genes. Development 1994; 120:827-41; PMID:7600960
161. Zallen JA, Wieschaus E. Patterned gene expression directs bipolar planar polarity in Drosophila. Dev Cell 2004; 6:343-55; PMID:15030758; http://dx.doi.org/10.1016/S1534-5807(04)00060-7
162. Tan JL, Ravid S, Spudich JA. Control of nonmusclemyosins by phosphorylation. Ann Rev Biochem 1992; 61:721-59; PMID:1497323; http://dx.doi.org/10.1146/annurev.bi.61.070192.003445
163. Nikolaidou KK, Barrett K. A Rho GTPase signaling pathway is used reiteratively in epithelial folding and potentially selects the outcome of Rho activation. Curr Biol: CB 2004; 14:1822-6; PMID:15498489; http://dx.doi.org/10.1016/j.cub.2004.09.080
164. Barrett K, Leptin M, Settleman J. The Rho GTPase and a putative RhoGEF mediate a signaling pathway for the cell shape changes in Drosophila gastrulation. Cell 1997; 91:905-15; PMID:9428514; http://dx.doi.org/10.1016/S0092-8674(00)80482-1
165. He B, Doubrovinski K, Polyakov O, Wieschaus E. Apical constriction drives tissue-scale hydrodynamic flow to mediate cell elongation. Nature 2014; 508:392-6; PMID:24590071; http://dx.doi.org/10.1038/nature13070
166. Gorfinkiel N, Blanchard GB, Adams RJ, Martinez Arias A. Mechanical control of global cell behavior during dorsal closure in Drosophila. Development 2009; 136:1889-98; PMID:19403661; http://dx.doi.org/10.1242/dev.030866
167. Solon J, Kaya-Copur A, Colombelli J, Brunner D. Pulsed forces timed by a ratchet-like mechanism drive directed tissue movement during dorsal closure. Cell 2009; 137:1331-42; PMID:19563762; http://dx.doi.org/10.1016/j.cell.2009.03.050
168. David DJ, Tishkina A, Harris TJ. The PAR complex regulates pulsed actomyosin contractions during amnioserosa apical constriction in Drosophila. Development 2010; 137:1645-55; PMID:20392741; http://dx.doi.org/10.1242/dev.044107
169. Harden N, Ricos M, Yee K, Sanny J, Langmann C, Yu H, Chia W, Lim L. Drac1 and Crumbs participate in amnioserosa morphogenesis during dorsal closure in Drosophila. J Cell Sci 2002; 115:2119-29; PMID:11973353
170. David DJ, Tishkina A, Harris TJ. The PAR complex regulates pulsed actomyosin contractions during amnioserosa apical constriction in Drosophila. Development 2010; 137:1645-55; PMID:20392741; http://dx.doi.org/10.1242/dev.044107
171. Baum B, Georgiou M. Dynamics of adherens junc tions in epithelial establishment, maintenance, and remodeling. J Cell Biol 2011; 192:907-17; PMID: 21422226; http://dx.doi.org/10.1083/jcb.201009141
172. Ngok SP, Geyer R, Liu M, Kourtidis A, Agrawal S, Wu C, Seerapu HR, Lewis-Tuffin LJ, Moodie KL, Huveldt D, et al. VEGF and Angiopoietin-1 exert opposing effects on cell junctions by regulating the Rho GEF Syx. J Cell Biol 2012; 199:1103-15; PMID:23253477; http://dx.doi.org/10.1083/jcb.201207009
173. Koh W, Mahan RD, Davis GE. Cdc42 and Rac1mediated endothelial lumen formation requires Pak2, Pak4 and Par3, and PKC-dependent signaling. J Cell Sci 2008; 121:989-1001; PMID:18319301; http://dx.doi.org/10.1242/jcs.020693
174. Gomes ER, Jani S, Gundersen GG. Nuclear move ment regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells. Cell 2005; 121:451-63; PMID:15882626; http://dx.doi.org/10.1016/j.cell.2005.02.022
175. Wang S, Watanabe T, Matsuzawa K, Katsumi A, Kakeno M, Matsui T, Ye F, Sato K, Murase K, Sugiyama I, et al. Tiam1 interaction with the PAR complex promotes talin-mediated Rac1 activation during polarized cell migration. J Cell Biol 2012; 199:331-45; PMID:23071154; http://dx.doi.org/10.1083/jcb.201202041
176. Pegtel DM, Ellenbroek SI, Mertens AE, van der Kammen RA, de Rooij J, Collard JG. The Par-Tiam1 complex controls persistent migration by stabilizing microtubule-dependent front-rear polarity. Curr Biol: CB 2007; 17:1623-34; PMID:17825562; http://dx.doi.org/10.1016/j.cub.2007.08.035
177. Nakayama M, Goto TM, Sugimoto M, Nishimura T, Shinagawa T, Ohno S, Amano M, Kaibuchi K. Rho kinase phosphorylates PAR-3 and disrupts PAR complex formation. Dev Cell 2008; 14:205-15; PMID:18267089; http://dx.doi.org/10.1016/j.devcel.2007.11.021
178. Raftopoulou M, Hall A. Cell migration: Rho GTPases lead the way. Dev Biol 2004; 265:23-32; PMID: 14697350; http://dx.doi.org/10.1016/j.ydbio.2003.06.003
179. Friedl P, Wolf K, Zegers MM. Rho-directed forces in collective migration. Nat Cell Biol 2014; 16:208-10; PMID:24576897; http://dx.doi.org/10.1038/ncb2923
180. Johnson DI. Cdc42: an essential Rho-type GTPase controlling eukaryotic cell polarity. Microbiol Mol Biol Rev: MMBR 1999; 63:54-105; PMID:10066831
181. Ory S, Gasman S. Rho GTPases and exocytosis: what are the molecular links? Semin Cell Dev Biol 2011; 22:27-32; PMID:21145407; http://dx.doi.org/10.1016/j.semcdb.2010.12.002
182. Mayor R, Theveneau E. The role of the non-canonical Wnt-planar cell polarity pathway in neural crest migration. Biochem J 2014; 457:19-26; PMID: 24325550; http://dx.doi.org/10.1042/BJ20131182
183. Tahirovic S, Bradke F. Neuronal polarity. Cold Spring Harbor Perspect Biol 2009; 1:a001644; PMID:20066106; http://dx.doi.org/10.1101/cshperspect.a001644
184. Macara IG. Par proteins: partners in polarization. Curr Biol: CB 2004; 14:R160-2; PMID:15027470; http://dx.doi.org/10.1016/j.cub.2004.01.048
185. Goldstein B, Macara IG. The PAR proteins: funda mental players in animal cell polarization. Dev Cell 2007; 13:609-22; PMID:17981131; http://dx.doi.org/10.1016/j.devcel.2007.10.007
186. Nance J, Zallen JA. Elaborating polarity: PAR pro teins and the cytoskeleton. Development 2011; 138:799-809; PMID:21303844; http://dx.doi.org/10.1242/dev.053538
187. Etienne-Manneville S, Hall A. Integrin-mediated acti vation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta. Cell 2001; 106:489-98; PMID:11525734; http://dx.doi.org/10.1016/S00928674(01)00471-8
188. Kolega J. Asymmetric distribution of myosin IIB in migrating endothelial cells is regulated by a rho dependent kinase and contributes to tail retraction. Mol Biol Cell 2003; 14:4745-57; PMID:12960430; http://dx.doi.org/10.1091/mbc.E03-04-0205
189. Worthylake RA, Lemoine S, Watson JM, Burridge K. RhoA is required for monocyte tail retraction during transendothelial migration. J Cell Biol 2001; 154:147-60; PMID:11448997; http://dx.doi.org/10.1083/jcb.200103048
190. Pertz O, Hodgson L, Klemke RL, Hahn KM. Spatio temporal dynamics of RhoA activity in migrating cells. Nature 2006; 440:1069-72; PMID:16547516; http://dx.doi.org/10.1038/nature04665
191. Machacek M, Hodgson L, Welch C, Elliott H, Pertz O, Nalbant P, Abell A, Johnson GL, Hahn KM, Dan user G. Coordination of Rho GTPase activities during cell protrusion. Nature 2009; 461:99-103; PMID: 19693013; http://dx.doi.org/10.1038/nature08242
192. El-Sibai M, Pertz O, Pang H, Yip SC, Lorenz M, Symons M, Condeelis JS, Hahn KM, Backer JM. RhoAROCK-mediated switching between Cdc42 and Rac1-dependent protrusion in MTLn3 carcinoma cells. Exp Cell Res 2008; 314:1540-52; PMID: 18316075; http://dx.doi.org/10.1016/j.yexcr.2008.01.016
193. Petrie RJ, Yamada KM. At the leading edge of three dimensional cell migration. J Cell Sci 2012; 125:5917-26; PMID:23378019; http://dx.doi.org/10.1242/jcs.093732
194. Osmani N, Peglion F, Chavrier P, Etienne-Manneville S.Cdc42 localization and cell polarity depend on membrane traffic. J Cell Biol 2010; 191:1261-9; PMID: 21173111; http://dx.doi.org/10.1083/jcb.201003091
195. Bahri S, Wang S, Conder R, Choy J, Vlachos S, Dong K, Merino C, Sigrist S, Molnar C, Yang X, et al. The leading edge during dorsal closure as a model for epithelial plasticity: pak is required for recruitment of the Scribble complex and septate junction formation. Development 2010; 137:2023-32; PMID:20501591; http://dx.doi.org/10.1242/dev.045088
196. Royer C, Lu X. Epithelial cell polarity: a major gate keeper against cancer? Cell Death Differ 2011; 18:1470-7; PMID:21617693; http://dx.doi.org/10.1038/cdd.2011.60
197. Xue B, Krishnamurthy K, Allred DC, Muthuswamy SK. Loss of Par3 promotes breast cancer metastasis by compromising cell-cell cohesion. Nat Cell Biol 2013; 15:189-200; PMID:23263278; http://dx.doi.org/10.1038/ncb2663
198. Zhan L, Rosenberg A, Bergami KC, Yu M, Xuan Z, Jaffe AB, Allred C, Muthuswamy SK. Deregulation of scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma. Cell 2008; 135:865-78; PMID:19041750; http://dx.doi.org/10.1016/j.cell.2008.09.045
199. Pearson HB, Perez-Mancera PA, Dow LE, Ryan A, Tennstedt P, Bogani D, Elsum I, Greenfield A, Tuve son DA, Simon R, et al. SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia. J Clin Invest 2011; 121:4257-67; PMID:21965329; http://dx.doi.org/10.1172/JCI58509
200. Feigin ME, Akshinthala SD, Araki K, Rosenberg AZ, Muthuswamy LB, Martin B, Lehmann BD, Berman HK, Pietenpol JA, Cardiff RD, et al. Mislocalization of the cell polarity protein scribble promotes mammary tumorigenesis and is associated with Basal breast cancer. Cancer Res 2014; 74:3180-94; PMID:24662921; http://dx.doi.org/10.1158/00085472.CAN-13-3415
201. Liu S, Li Y, Qi W, Zhao Y, Huang A, Sheng W, Lei B, Lin P, Zhu H, Li W, et al. Expression of Tiam1 predicts lymph node metastasis and poor survival of lung adenocarcinoma patients. Diagn Pathol 2014; 9:69; PMID:24661909; http://dx.doi.org/10.1186/1746-1596-9-69
202. Wang S, Li S, Yang X, Yang S, Liu S, Liu B, Liu J. Elevated expression of T-lymphoma invasion and metastasis inducing factor 1 in squamous-cell carcinoma of the head and neck and its clinical significance. Eur J Cancer 2014; 50:379-87; PMID:24189000; http://dx.doi.org/10.1016/j.ejca.2013.10.003
203. Qi Y, Huang B, Yu L, Wang Q, Lan G, Zhang Q. Prognostic value of Tiam1 and Rac1 overexpression in nasopharyngeal carcinoma. ORL; J Oto-RhinoLaryngol Its Relat Spec 2009; 71:163-71; PMID: 19506399; http://dx.doi.org/10.1159/00022344015
204. Liu N, Tang LL, Sun Y, Cui RX, Wang HY, Huang BJ, He QM, Jiang W, Ma J. MiR-29c suppresses invasion and metastasis by targeting TIAM1 in nasopharyngeal carcinoma. Cancer Lett 2013; 329:181-8; PMID:23142282; http://dx.doi.org/10.1016/j.canlet.2012.10.032
205. Lane J, Martin TA, Mansel RE, Jiang WG. The expression and prognostic value of the guanine nucleotide exchange factors (GEFs) Trio, Vav1 and TIAM-1 in human breast cancer. Int Semin Surg Oncol: ISSO 2008; 5:23; PMID:18925966; http://dx.doi.org/10.1186/1477-7800-5-23