Establishment of epithelial polarity - GEF who's minding the GAP?

Journal of Cell Science

Volumn 127, Issue 15, 2014, Pages 3205-3215

  Ngok, Siu P ^a   Lin, Wan Hsin ^a   Anastasiadis, Panos Z ^a  

^a MAYO CLINIC   (United States)

Author keywords

Cell adhesion; Cell polarity; Crumbs; Par3; Rho GTPase; Scribble

Indexed keywords

DNA BINDING PROTEIN; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; SLC2A4RG PROTEIN, HUMAN; TRANSCRIPTION FACTOR;

ANIMAL; CARCINOGENESIS; CELL CYCLE; CELL MOTION; CELL POLARITY; EPITHELIUM CELL; HUMAN; METABOLISM; MORPHOGENESIS; PHYSIOLOGY;

ANIMALS; CARCINOGENESIS; CELL CYCLE; CELL MOVEMENT; CELL POLARITY; DNA-BINDING PROTEINS; EPITHELIAL CELLS; GTPASE-ACTIVATING PROTEINS; HUMANS; MORPHOGENESIS; TRANSCRIPTION FACTORS;

EID: 84905473528     PISSN: 00219533     EISSN: 14779137     Source Type: Journal    
DOI: 10.1242/jcs.153197     Document Type: Note

References (219)

1. Adachi, M., Hamazaki, Y., Kobayashi, Y., Itoh, M., Tsukita, S., Furuse, M. and Tsukita, S. (2009). Similar and distinct properties of MUPP1 and Patj, two homologous PDZ domain-containing tight-junction proteins. Mol. Cell. Biol. 29, 2372-2389.
2. Adams, C. L. and Nelson, W. J. (1998). Cytomechanics of cadherin-mediated cell-cell adhesion. Curr. Opin. Cell Biol. 10, 572-577.
3. Adams, C. L., Chen, Y. T., Smith, S. J. and Nelson, W. J. (1998). Mechanisms of epithelial cell-cell adhesion and cell compaction revealed by high-resolution tracking of E-cadherin-green fluorescent protein. J. Cell Biol. 142, 1105-1119.
4. Aijaz, S., D'Atri, F., Citi, S., Balda, M. S. and Matter, K. (2005). Binding of GEFH1 to the tight junction-associated adaptor cingulin results in inhibition of Rho signaling and G1/S phase transition. Dev. Cell 8, 777-786.
5. Al-Dosari, M. S., Al-Owain, M., Tulbah, M., Kurdi, W., Adly, N., Al-Hemidan, A., Masoodi, T. A., Albash, B. and Alkuraya, F. S. (2013). Mutation in MPDZ causes severe congenital hydrocephalus. J. Med. Genet. 50, 54-58.
6. Anderson, D. C., Gill, J. S., Cinalli, R. M. and Nance, J. (2008). Polarization of the C. elegans embryo by RhoGAP-mediated exclusion of PAR-6 from cell contacts. Science 320, 1771-1774.
7. Apodaca, G., Gallo, L. I. and Bryant, D. M. (2012). Role of membrane traffic in the generation of epithelial cell asymmetry. Nat. Cell Biol. 14, 1235-1243.
8. Audebert, S., Navarro, C., Nourry, C., Chasserot-Golaz, S., Lécine, P., Bellaiche, Y., Dupont, J. L., Premont, R. T., Sempéré, C., Strub, J. M. et al. (2004). Mammalian Scribble forms a tight complex with the betaPIX exchange factor. Curr. Biol. 14, 987-995.
9. Baas, A. F., Kuipers, J., van der Wel, N. N., Batlle, E., Koerten, H. K., Peters, P. J. and Clevers, H. C. (2004). Complete polarization of single intestinal epithelial cells upon activation of LKB1 by STRAD. Cell 116, 457-466.
10. Benais-Pont, G., Punn, A., Flores-Maldonado, C., Eckert, J., Raposo, G., Fleming, T. P., Cereijido, M., Balda, M. S. and Matter, K. (2003). Identification of a tight junction-associated guanine nucleotide exchange factor that activates Rho and regulates paracellular permeability. J. Cell Biol. 160, 729-740.
11. Betschinger, J., Mechtler, K. and Knoblich, J. A. (2003). The Par complex directs asymmetric cell division by phosphorylating the cytoskeletal protein Lgl. Nature 422, 326-330.
12. Betschinger, J., Eisenhaber, F. and Knoblich, J. A. (2005). Phosphorylationinduced autoinhibition regulates the cytoskeletal protein Lethal (2) giant larvae. Curr. Biol. 15, 276-282.
13. Bilder, D. and Perrimon, N. (2000). Localization of apical epithelial determinants by the basolateral PDZ protein Scribble. Nature 403, 676-680.
14. Bilder, D., Li, M. and Perrimon, N. (2000). Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. Science 289, 113-116.
15. Bilder, D., Schober, M. and Perrimon, N. (2003). Integrated activity of PDZ protein complexes regulates epithelial polarity. Nat. Cell Biol. 5, 53-58.
16. Binamé, F., Sakry, D., Dimou, L., Jolivel, V. and Trotter, J. (2013). NG2 regulates directional migration of oligodendrocyte precursor cells via Rho GTPases and polarity complex proteins. J. Neurosci. 33, 10858-10874.
17. Bray, K., Brakebusch, C. and Vargo-Gogola, T. (2011). The Rho GTPase Cdc42 is required for primary mammary epithelial cell morphogenesis in vitro. Small GTPases 2, 247-258.
18. Bryant, D. M., Datta, A., Rodríguez-Fraticelli, A. E., Peränen, J., Martín-Belmonte, F. and Mostov, K. E. (2010). A molecular network for de novo generation of the apical surface and lumen. Nat. Cell Biol. 12, 1035-1045.
19. Chalmers, A. D., Pambos, M., Mason, J., Lang, S., Wylie, C. and Papalopulu, N. (2005). aPKC, Crumbs3 and Lgl2 control apicobasal polarity in early vertebrate development. Development 132, 977-986.
20. Chen, X. and Macara, I. G. (2005). Par-3 controls tight junction assembly through the Rac exchange factor Tiam1. Nat. Cell Biol. 7, 262-269.
21. Chen, C. L., Gajewski, K. M., Hamaratoglu, F., Bossuyt, W., Sansores-Garcia, L., Tao, C. and Halder, G. (2010). The apical-basal cell polarity determinant Crumbs regulates Hippo signaling in Drosophila. Proc. Natl. Acad. Sci. USA 107, 15810-15815.
22. Chen, S., Chen, J., Shi, H., Wei, M., Castaneda-Castellanos, D. R., Bultje, R. S., Pei, X., Kriegstein, A. R., Zhang, M. and Shi, S. H. (2013). Regulation of microtubule stability and organization by mammalian Par3 in specifying neuronal polarity. Dev. Cell 24, 26-40.
23. Cook, D. R., Rossman, K. L. and Der, C. J. (2013). Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease. Oncogene.
24. Dachsel, J. C., Ngok, S. P., Lewis-Tuffin, L. J., Kourtidis, A., Geyer, R., Johnston, L., Feathers, R. and Anastasiadis, P. Z. (2013). The Rho guanine nucleotide exchange factor Syx regulates the balance of dia and ROCK activities to promote polarized-cancer-cell migration. Mol. Cell. Biol. 33, 4909-4918.
25. den Hollander, A. I., ten Brink, J. B., de Kok, Y. J., van Soest, S., van den Born, L. I., van Driel, M. A., van de Pol, D. J., Payne, A. M., Bhattacharya, S. S., Kellner, U. et al. (1999). Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12). Nat. Genet. 23, 217-221.
26. den Hollander, A. I., Ghiani, M., de Kok, Y. J., Wijnholds, J., Ballabio, A., Cremers, F. P. and Broccoli, V. (2002). Isolation of Crb1, a mouse homologue of Drosophila crumbs, and analysis of its expression pattern in eye and brain. Mech. Dev. 110, 203-207.
27. Doerflinger, H., Vogt, N., Torres, I. L., Mirouse, V., Koch, I., Nüsslein-Volhard, C. and St Johnston, D. (2010). Bazooka is required for polarisation of the Drosophila anterior-posterior axis. Development 137, 1765-1773.
28. Dow, L. E., Brumby, A. M., Muratore, R., Coombe, M. L., Sedelies, K. A., Trapani, J. A., Russell, S. M., Richardson, H. E. and Humbert, P. O. (2003). hScrib is a functional homologue of the Drosophila tumour suppressor Scribble. Oncogene 22, 9225-9230.
29. Dow, L. E., Kauffman, J. S., Caddy, J., Zarbalis, K., Peterson, A. S., Jane, S. M., Russell, S. M. and Humbert, P. O. (2007). The tumour-suppressor Scribble dictates cell polarity during directed epithelial migration: regulation of Rho GTPase recruitment to the leading edge. Oncogene 26, 2272-2282.
30. Eastburn, D. J., Zegers, M. M. and Mostov, K. E. (2012). Scrib regulates HGFmediated epithelial morphogenesis and is stabilized by Sgt1-HSP90. J. Cell Sci. 125, 4147-4157.
31. Ebnet, K., Suzuki, A., Horikoshi, Y., Hirose, T., Meyer Zu Brickwedde, M. K., Ohno, S. and Vestweber, D. (2001). The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM). EMBO J. 20, 3738-3748.
32. Ebnet, K., Aurrand-Lions, M., Kuhn, A., Kiefer, F., Butz, S., Zander, K., Meyer zu Brickwedde, M. K., Suzuki, A., Imhof, B. A. and Vestweber, D. (2003). The junctional adhesion molecule (JAM) family members JAM-2 and JAM-3 associate with the cell polarity protein PAR-3: a possible role for JAMs in endothelial cell polarity. J. Cell Sci. 116, 3879-3891.
33. Elbert, M., Cohen, D. and Müsch, A. (2006). PAR1b promotes cell-cell adhesion and inhibits dishevelled-mediated transformation of Madin-Darby canine kidney cells. Mol. Biol. Cell 17, 3345-3355.
34. Ernkvist, M., Luna Persson, N., Audebert, S., Lecine, P., Sinha, I., Liu, M., Schlueter, M., Horowitz, A., Aase, K., Weide, T. et al. (2009). The Amot/Patj/Syx signaling complex spatially controls RhoA GTPase activity in migrating endothelial cells. Blood 113, 244-253.
35. Estévez, M. A., Henderson, J. A., Ahn, D., Zhu, X. R., Poschmann, G., Lübbert, H., Marx, R. and Baraban, J. M. (2008). The neuronal RhoA GEF, Tech, interacts with the synaptic multi-PDZ-domain-containing protein, MUPP1. J. Neurochem. 106, 1287-1297.
36. Etemad-Moghadam, B., Guo, S. and Kemphues, K. J. (1995). Asymmetrically distributed PAR-3 protein contributes to cell polarity and spindle alignment in early C. elegans embryos. Cell 83, 743-752.
37. Etienne-Manneville, S. and Hall, A. (2002). Rho GTPases in cell biology. Nature 420, 629-635.
38. Fletcher, G. C., Lucas, E. P., Brain, R., Tournier, A. and Thompson, B. J. (2012). Positive feedback and mutual antagonism combine to polarize Crumbs in the Drosophila follicle cell epithelium. Curr. Biol. 22, 1116-1122.
39. Fogg, V. C., Liu, C. J. and Margolis, B. (2005). Multiple regions of Crumbs3 are required for tight junction formation in MCF10A cells. J. Cell Sci. 118, 2859-2869.
40. Fukuhara, A., Shimizu, K., Kawakatsu, T., Fukuhara, T. and Takai, Y. (2003). Involvement of nectin-activated Cdc42 small G protein in organization of adherens and tight junctions in Madin-Darby canine kidney cells. J. Biol. Chem. 278, 51885-51893.
41. Gao, L., Joberty, G. and Macara, I. G. (2002). Assembly of epithelial tight junctions is negatively regulated by Par6. Curr. Biol. 12, 221-225.
42. García-Mata, R. and Burridge, K. (2007). Catching a GEF by its tail. Trends Cell Biol. 17, 36-43.
43. Garcia-Mata, R., Boulter, E. and Burridge, K. (2011). The 'invisible hand': regulation of RHO GTPases by RHOGDIs. Nat. Rev. Mol. Cell Biol. 12, 493-504.
44. Garnaas, M. K., Moodie, K. L., Liu, M. L., Samant, G. V., Li, K., Marx, R., Baraban, J. M., Horowitz, A. and Ramchandran, R. (2008). Syx, a RhoA guanine exchange factor, is essential for angiogenesis in vivo. Circ. Res. 103, 710-716.
45. Gateff, E. (1978). Malignant neoplasms of genetic origin in Drosophila melanogaster. Science 200, 1448-1459.
46. Georgiou, M., Marinari, E., Burden, J. and Baum, B. (2008). Cdc42, Par6, and aPKC regulate Arp2/3-mediated endocytosis to control local adherens junction stability. Curr. Biol. 18, 1631-1638.
47. Gloerich, M., ten Klooster, J. P., Vliem, M. J., Koorman, T., Zwartkruis, F. J., Clevers, H. and Bos, J. L. (2012). Rap2A links intestinal cell polarity to brush border formation. Nat. Cell Biol. 14, 793-801.
48. Grawe, F., Wodarz, A., Lee, B., Knust, E. and Skaer, H. (1996). The Drosophila genes crumbs and stardust are involved in the biogenesis of adherens junctions. Development 122, 951-959.
49. Grifoni, D., Garoia, F., Bellosta, P., Parisi, F., De Biase, D., Collina, G., Strand, D., Cavicchi, S. and Pession, A. (2007). aPKCzeta cortical loading is associated with Lgl cytoplasmic release and tumor growth in Drosophila and human epithelia. Oncogene 26, 5960-5965.
50. Grise, F., Bidaud, A. and Moreau, V. (2009). Rho GTPases in hepatocellular carcinoma. Biochim. Biophys. Acta 1795, 137-151.
51. Grzeschik, N. A., Parsons, L. M., Allott, M. L., Harvey, K. F. and Richardson, H. E. (2010). Lgl, aPKC, and Crumbs regulate the Salvador/Warts/Hippo pathway through two distinct mechanisms. Curr. Biol. 20, 573-581.
52. Guillemot, L., Paschoud, S., Jond, L., Foglia, A. and Citi, S. (2008). Paracingulin regulates the activity of Rac1 and RhoA GTPases by recruiting Tiam1 and GEF-H1 to epithelial junctions. Mol. Biol. Cell 19, 4442-4453.
53. Guillemot, L., Guerrera, D., Spadaro, D., Tapia, R., Jond, L. and Citi, S. (2014). MgcRacGAP interacts with cingulin and paracingulin to regulate rac1 activation and development of the tight junction barrier during epithelial junction assembly. Mol. Biol. Cell.
54. Guo, S. and Kemphues, K. J. (1995). par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed. Cell 81, 611-620.
55. Hamazaki, Y., Itoh, M., Sasaki, H., Furuse, M. and Tsukita, S. (2002). Multi-PDZ domain protein 1 (MUPP1) is concentrated at tight junctions through its possible interaction with claudin-1 and junctional adhesion molecule. J. Biol. Chem. 277, 455-461.
56. Hayase, J., Kamakura, S., Iwakiri, Y., Yamaguchi, Y., Izaki, T., Ito, T. and Sumimoto, H. (2013). The WD40 protein Morg1 facilitates Par6-aPKC binding to Crb3 for apical identity in epithelial cells. J. Cell Biol. 200, 635-650.
57. Henrique, D. and Schweisguth, F. (2003). Cell polarity: the ups and downs of the Par6/aPKC complex. Curr. Opin. Genet. Dev. 13, 341-350.
58. Herranz, H., Stamataki, E., Feiguin, F. and Milán, M. (2006). Self-refinement of Notch activity through the transmembrane protein Crumbs: modulation of gamma-secretase activity. EMBO Rep. 7, 297-302.
59. Hirose, T., Izumi, Y., Nagashima, Y., Tamai-Nagai, Y., Kurihara, H., Sakai, T., Suzuki, Y., Yamanaka, T., Suzuki, A., Mizuno, K. et al. (2002). Involvement of ASIP/PAR-3 in the promotion of epithelial tight junction formation. J. Cell Sci. 115, 2485-2495.
60. Horikoshi, Y., Suzuki, A., Yamanaka, T., Sasaki, K., Mizuno, K., Sawada, H., Yonemura, S. and Ohno, S. (2009). Interaction between PAR-3 and the aPKCPAR-6 complex is indispensable for apical domain development of epithelial cells. J. Cell Sci. 122, 1595-1606.
61. Hung, T. J. and Kemphues, K. J. (1999). PAR-6 is a conserved PDZ domaincontaining protein that colocalizes with PAR-3 in Caenorhabditis elegans embryos. Development 126, 127-135.
62. Hurd, T. W., Gao, L., Roh, M. H., Macara, I. G. and Margolis, B. (2003). Direct interaction of two polarity complexes implicated in epithelial tight junction assembly. Nat. Cell Biol. 5, 137-142.
63. Hurov, J. B., Watkins, J. L. and Piwnica-Worms, H. (2004). Atypical PKC phosphorylates PAR-1 kinases to regulate localization and activity. Curr. Biol. 14, 736-741.
64. Hutterer, A., Betschinger, J., Petronczki, M. and Knoblich, J. A. (2004). Sequential roles of Cdc42, Par-6, aPKC, and Lgl in the establishment of epithelial polarity during Drosophila embryogenesis. Dev. Cell 6, 845-854.
65. Iden, S. and Collard, J. G. (2008). Crosstalk between small GTPases and polarity proteins in cell polarization. Nat. Rev. Mol. Cell Biol. 9, 846-859.
66. Iden, S., Misselwitz, S., Peddibhotla, S. S., Tuncay, H., Rehder, D., Gerke, V., Robenek, H., Suzuki, A. and Ebnet, K. (2012). aPKC phosphorylates JAM-A at Ser285 to promote cell contact maturation and tight junction formation. J. Cell Biol. 196, 623-639.
67. Ishiuchi, T. and Takeichi, M. (2011). Willin and Par3 cooperatively regulate epithelial apical constriction through aPKC-mediated ROCK phosphorylation. Nat. Cell Biol. 13, 860-866.
68. Itoh, M., Sasaki, H., Furuse, M., Ozaki, H., Kita, T. and Tsukita, S. (2001). Junctional adhesion molecule (JAM) binds to PAR-3: a possible mechanism for the recruitment of PAR-3 to tight junctions. J. Cell Biol. 154, 491-498.
69. Itoh, M., Tsukita, S., Yamazaki, Y. and Sugimoto, H. (2012). Rho GTP exchange factor ARHGEF11 regulates the integrity of epithelial junctions by connecting ZO-1 and RhoA-myosin II signaling. Proc. Natl. Acad. Sci. USA 109, 9905-9910.
70. Ivanov, A. I., Hunt, D., Utech, M., Nusrat, A. and Parkos, C. A. (2005). Differential roles for actin polymerization and a myosin II motor in assembly of the epithelial apical junctional complex. Mol. Biol. Cell 16, 2636-2650.
71. Ivanov, A. I., Young, C., Den Beste, K., Capaldo, C. T., Humbert, P. O., Brennwald, P., Parkos, C. A. and Nusrat, A. (2010). Tumor suppressor scribble regulates assembly of tight junctions in the intestinal epithelium. Am. J. Pathol. 176, 134-145.
72. Izumi, Y., Hirose, T., Tamai, Y., Hirai, S., Nagashima, Y., Fujimoto, T., Tabuse, Y., Kemphues, K. J. and Ohno, S. (1998). An atypical PKC directly associates and colocalizes at the epithelial tight junction with ASIP, a mammalian homologue of Caenorhabditis elegans polarity protein PAR-3. J. Cell Biol. 143, 95-106.
73. Joberty, G., Petersen, C., Gao, L. and Macara, I. G. (2000). The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nat. Cell Biol. 2, 531-539.
74. Johansson, A., Driessens, M. and Aspenström, P. (2000). The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1. J. Cell Sci. 113, 3267-3275.
75. Johnston, C. A., Hirono, K., Prehoda, K. E. and Doe, C. Q. (2009). Identification of an Aurora-A/PinsLINKER/Dlg spindle orientation pathway using induced cell polarity in S2 cells. Cell 138, 1150-1163.
76. Jou, T. S. and Nelson, W. J. (1998). Effects of regulated expression of mutant RhoA and Rac1 small GTPases on the development of epithelial (MDCK) cell polarity. J. Cell Biol. 142, 85-100.
77. Jou, T. S., Schneeberger, E. E. and Nelson, W. J. (1998). Structural and functional regulation of tight junctions by RhoA and Rac1 small GTPases. J. Cell Biol. 142, 101-115.
78. Jurgens, G., Wieschaus, E., Nusslein-Volhard, C. and Kluding, H. (1984). Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster. Roux's Arch. Develop. Biol. 193, 283-295.
79. Kallay, L. M., McNickle, A., Brennwald, P. J., Hubbard, A. L. and Braiterman, L. T. (2006). Scribble associates with two polarity proteins, Lgl2 and Vangl2, via distinct molecular domains. J. Cell. Biochem. 99, 647-664.
80. Kawakatsu, T., Shimizu, K., Honda, T., Fukuhara, T., Hoshino, T. and Takai, Y. (2002). Trans-interactions of nectins induce formation of filopodia and Lamellipodia through the respective activation of Cdc42 and Rac small G proteins. J. Biol. Chem. 277, 50749-50755.
81. Kawazu, M., Ueno, T., Kontani, K., Ogita, Y., Ando, M., Fukumura, K., Yamato, A., Soda, M., Takeuchi, K., Miki, Y. et al. (2013). Transforming mutations of RAC guanosine triphosphatases in human cancers. Proc. Natl. Acad. Sci. USA 110, 3029-3034.
82. Kemphues, K. (2000). PARsing embryonic polarity. Cell 101, 345-348.
83. Kemphues, K. J., Priess, J. R., Morton, D. G. and Cheng, N. S. (1988). Identification of genes required for cytoplasmic localization in early C. elegans embryos. Cell 52, 311-320.
84. Kempkens, O., Médina, E., Fernandez-Ballester, G., Ozüyaman, S., Le Bivic, A., Serrano, L. and Knust, E. (2006). Computer modelling in combination with in vitro studies reveals similar binding affinities of Drosophila Crumbs for the PDZ domains of Stardust and DmPar-6. Eur. J. Cell Biol. 85, 753-767.
85. Kim, S. H., Li, Z. and Sacks, D. B. (2000). E-cadherin-mediated cell-cell attachment activates Cdc42. J. Biol. Chem. 275, 36999-37005.
86. Klebes, A. and Knust, E. (2000). A conserved motif in Crumbs is required for Ecadherin localisation and zonula adherens formation in Drosophila. Curr. Biol. 10, 76-85.
87. Klein, S., Partisani, M., Franco, M. and Luton, F. (2008). EFA6 facilitates the assembly of the tight junction by coordinating an Arf6-dependent and -independent pathway. J. Biol. Chem. 283, 30129-30138.
88. Knust, E. and Bossinger, O. (2002). Composition and formation of intercellular junctions in epithelial cells. Science 298, 1955-1959.
89. Kodama, A., Takaishi, K., Nakano, K., Nishioka, H. and Takai, Y. (1999). Involvement of Cdc42 small G protein in cell-cell adhesion, migration and morphology of MDCK cells. Oncogene 18, 3996-4006.
90. Koh, Y. H., Popova, E., Thomas, U., Griffith, L. C. and Budnik, V. (1999). Regulation of DLG localization at synapses by CaMKII-dependent phosphorylation. Cell 98, 353-363.
91. Krahn, M. P., Bückers, J., Kastrup, L. and Wodarz, A. (2010). Formation of a Bazooka-Stardust complex is essential for plasma membrane polarity in epithelia. J. Cell Biol. 190, 751-760.
92. Lamarche, N. and Hall, A. (1994). GAPs for rho-related GTPases. Trends Genet. 10, 436-440.
93. Lambert, J. M., Lambert, Q. T., Reuther, G. W., Malliri, A., Siderovski, D. P., Sondek, J., Collard, J. G. and Der, C. J. (2002). Tiam1 mediates Ras activation of Rac by a PI(3)K-independent mechanism. Nat. Cell Biol. 4, 621-625.
94. Laprise, P., Viel, A. and Rivard, N. (2004). Human homolog of disc-large is required for adherens junction assembly and differentiation of human intestinal epithelial cells. J. Biol. Chem. 279, 10157-10166.
95. Latorre, I. J., Roh, M. H., Frese, K. K., Weiss, R. S., Margolis, B. and Javier, R. T. (2005). Viral oncoprotein-induced mislocalization of select PDZ proteins disrupts tight junctions and causes polarity defects in epithelial cells. J. Cell Sci. 118, 4283-4293.
96. Lee, J. L. and Streuli, C. H. (2014). Integrins and epithelial cell polarity. J. Cell Sci. 127, 3217-3225.
97. Lemmers, C., Médina, E., Delgrossi, M. H., Michel, D., Arsanto, J. P. and Le Bivic, A. (2002). hINADl/PATJ, a homolog of discs lost, interacts with crumbs and localizes to tight junctions in human epithelial cells. J. Biol. Chem. 277, 25408-25415.
98. Lemmers, C., Michel, D., Lane-Guermonprez, L., Delgrossi, M. H., Médina, E., Arsanto, J. P. and Le Bivic, A. (2004). CRB3 binds directly to Par6 and regulates the morphogenesis of the tight junctions in mammalian epithelial cells. Mol. Biol. Cell 15, 1324-1333.
99. Lin, D., Edwards, A. S., Fawcett, J. P., Mbamalu, G., Scott, J. D. and Pawson, T. (2000). A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity. Nat. Cell Biol. 2, 549-552.
100. Ling, C., Zuo, D., Xue, B., Muthuswamy, S. and Muller, W. J. (2010). A novel role for 14-3-3sigma in regulating epithelial cell polarity. Genes Dev. 24, 947-956.
101. Liu, M. and Horowitz, A. (2006). A PDZ-binding motif as a critical determinant of Rho guanine exchange factor function and cell phenotype. Mol. Biol. Cell 17, 1880-1887.
102. Liu, X. F., Ishida, H., Raziuddin, R. and Miki, T. (2004). Nucleotide exchange factor ECT2 interacts with the polarity protein complex Par6/Par3/protein kinase Czeta (PKCzeta) and regulates PKCzeta activity. Mol. Cell. Biol. 24, 6665-6675.
103. Liu, X. F., Ohno, S. and Miki, T. (2006). Nucleotide exchange factor ECT2 regulates epithelial cell polarity. Cell. Signal. 18, 1604-1615.
104. Lohia, M., Qin, Y. and Macara, I. G. (2012). The Scribble polarity protein stabilizes E-cadherin/p120-catenin binding and blocks retrieval of E-cadherin to the Golgi. PLoS ONE 7, e51130.
105. Luton, F., Klein, S., Chauvin, J. P., Le Bivic, A., Bourgoin, S., Franco, M. and Chardin, P. (2004). EFA6, exchange factor for ARF6, regulates the actin cytoskeleton and associated tight junction in response to E-cadherin engagement. Mol. Biol. Cell 15, 1134-1145.
106. Macara, I. G. (2004). Parsing the polarity code. Nat. Rev. Mol. Cell Biol. 5, 220-231.
107. Macia, E., Luton, F., Partisani, M., Cherfils, J., Chardin, P. and Franco, M. (2004). The GDP-bound form of Arf6 is located at the plasma membrane. J. Cell Sci. 117, 2389-2398.
108. Mack, N. A., Porter, A. P., Whalley, H. J., Schwarz, J. P., Jones, R. C., Khaja, A. S., Bjartell, A., Anderson, K. I. and Malliri, A. (2012). β2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity. Nat. Cell Biol. 14, 1169-1180.
109. Makarova, O., Roh, M. H., Liu, C. J., Laurinec, S. and Margolis, B. (2003). Mammalian Crumbs3 is a small transmembrane protein linked to protein associated with Lin-7 (Pals1). Gene 302, 21-29.
110. Mantovani, F. and Banks, L. (2003). Regulation of the discs large tumor suppressor by a phosphorylation-dependent interaction with the beta-TrCP ubiquitin ligase receptor. J. Biol. Chem. 278, 42477-42486.
111. Martin-Belmonte, F., Gassama, A., Datta, A., Yu, W., Rescher, U., Gerke, V. and Mostov, K. (2007). PTEN-mediated apical segregation of phosphoinositides controls epithelial morphogenesis through Cdc42. Cell 128, 383-397.
112. Mathew, D., Gramates, L. S., Packard, M., Thomas, U., Bilder, D., Perrimon, N., Gorczyca, M. and Budnik, V. (2002). Recruitment of scribble to the synaptic scaffolding complex requires GUK-holder, a novel DLG binding protein. Curr. Biol. 12, 531-539.
113. McCaffrey, L. M. and Macara, I. G. (2009). Widely conserved signaling pathways in the establishment of cell polarity. Cold Spring Harb. Perspect. Biol. 1, a001370.
114. McClatchey, A. I. (2014). ERM proteins at a glance. J. Cell Sci. 127, 3199-3204.
115. Mechler, B. M., McGinnis, W. and Gehring, W. J. (1985). Molecular cloning of lethal(2)giant larvae, a recessive oncogene of Drosophila melanogaster. EMBO J. 4, 1551-1557.
116. Meller, N., Merlot, S. and Guda, C. (2005). CZH proteins: a new family of Rho-GEFs. J. Cell Sci. 118, 4937-4946.
117. Mertens, A. E., Rygiel, T. P., Olivo, C., van der Kammen, R. and Collard, J. G. (2005). The Rac activator Tiam1 controls tight junction biogenesis in keratinocytes through binding to and activation of the Par polarity complex. J. Cell Biol. 170, 1029-1037.
118. Mertens, A. E., Pegtel, D. M. and Collard, J. G. (2006). Tiam1 takes PARt in cell polarity. Trends Cell Biol. 16, 308-316.
119. Métais, J. Y., Navarro, C., Santoni, M. J., Audebert, S. and Borg, J. P. (2005). hScrib interacts with ZO-2 at the cell-cell junctions of epithelial cells. FEBS Lett. 579, 3725-3730.
120. Michel, D., Arsanto, J. P., Massey-Harroche, D., Béclin, C., Wijnholds, J. and Le Bivic, A. (2005). PATJ connects and stabilizes apical and lateral components of tight junctions in human intestinal cells. J. Cell Sci. 118, 4049-4057.
121. Miura, K., Nam, J. M., Kojima, C., Mochizuki, N. and Sabe, H. (2009). EphA2 engages Git1 to suppress Arf6 activity modulating epithelial cell-cell contacts. Mol. Biol. Cell 20, 1949-1959.
122. Mizuno, K., Suzuki, A., Hirose, T., Kitamura, K., Kutsuzawa, K., Futaki, M., Amano, Y. and Ohno, S. (2003). Self-association of PAR-3-mediated by the conserved N-terminal domain contributes to the development of epithelial tight junctions. J. Biol. Chem. 278, 31240-31250.
123. Montcouquiol, M., Rachel, R. A., Lanford, P. J., Copeland, N. G., Jenkins, N. A. and Kelley, M. W. (2003). Identification of Vangl2 and Scrb1 as planar polarity genes in mammals. Nature 423, 173-177.
124. Moon, S. Y. and Zheng, Y. (2003). Rho GTPase-activating proteins in cell regulation. Trends Cell Biol. 13, 13-22.
125. Morais-de-Sá, E., Mirouse, V. and St Johnston, D. (2010). aPKC phosphorylation of Bazooka defines the apical/lateral border in Drosophila epithelial cells. Cell 141, 509-523.
126. Müller, H. A. and Wieschaus, E. (1996). armadillo, bazooka, and stardust are critical for early stages in formation of the zonula adherens and maintenance of the polarized blastoderm epithelium in Drosophila. J. Cell Biol. 134, 149-163.
127. Murdoch, J. N., Henderson, D. J., Doudney, K., Gaston-Massuet, C., Phillips, H. M., Paternotte, C., Arkell, R., Stanier, P. and Copp, A. J. (2003). Disruption of scribble (Scrb1) causes severe neural tube defects in the circletail mouse. Hum. Mol. Genet. 12, 87-98.
128. Müsch, A., Cohen, D., Yeaman, C., Nelson, W. J., Rodriguez-Boulan, E. and Brennwald, P. J. (2002). Mammalian homolog of Drosophila tumor suppressor lethal (2) giant larvae interacts with basolateral exocytic machinery in Madin-Darby canine kidney cells. Mol. Biol. Cell 13, 158-168.
129. Nagai-Tamai, Y., Mizuno, K., Hirose, T., Suzuki, A. and Ohno, S. (2002). Regulated protein-protein interaction between aPKC and PAR-3 plays an essential role in the polarization of epithelial cells. Genes Cells 7, 1161-1171.
130. Nakagawa, M., Fukata, M., Yamaga, M., Itoh, N. and Kaibuchi, K. (2001). Recruitment and activation of Rac1 by the formation of E-cadherin-mediated cell-cell adhesion sites. J. Cell Sci. 114, 1829-1838.
131. Nakajima, H. and Tanoue, T. (2011). Lulu2 regulates the circumferential actomyosin tensile system in epithelial cells through p114RhoGEF. J. Cell Biol. 195, 245-261.
132. Nam, S. C. and Choi, K. W. (2003). Interaction of Par-6 and Crumbs complexes is essential for photoreceptor morphogenesis in Drosophila. Development 130, 4363-4372.
133. Nam, S. C. and Choi, K. W. (2006). Domain-specific early and late function of Dpatj in Drosophila photoreceptor cells. Dev. Dyn. 235, 1501-1507.
134. Narayan, N., Massimi, P. and Banks, L. (2009). CDK phosphorylation of the discs large tumour suppressor controls its localisation and stability. J. Cell Sci. 122, 65-74.
135. Navarro, C., Nola, S., Audebert, S., Santoni, M. J., Arsanto, J. P., Ginestier, C., Marchetto, S., Jacquemier, J., Isnardon, D., Le Bivic, A. et al. (2005). Junctional recruitment of mammalian Scribble relies on E-cadherin engagement. Oncogene 24, 4330-4339.
136. Ngok, S. P., Geyer, R., Liu, M., Kourtidis, A., Agrawal, S., Wu, C., Seerapu, H. R., Lewis-Tuffin, L. J., Moodie, K. L., Huveldt, D. et al. (2012). VEGF and Angiopoietin-1 exert opposing effects on cell junctions by regulating the Rho GEF Syx. J. Cell Biol. 199, 1103-1115.
137. Ngok, S. P., Geyer, R., Kourtidis, A., Mitin, N., Feathers, R., Der, C. and Anastasiadis, P. Z. (2013). TEM4 is a junctional Rho GEF required for cell-cell adhesion, monolayer integrity and barrier function. J. Cell Sci. 126, 3271-3277.
138. Nimnual, A. S., Taylor, L. J. and Bar-Sagi, D. (2003). Redox-dependent downregulation of Rho by Rac. Nat. Cell Biol. 5, 236-241.
139. Nishimura, T., Yamaguchi, T., Kato, K., Yoshizawa, M., Nabeshima, Y., Ohno, S., Hoshino, M. and Kaibuchi, K. (2005). PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1. Nat. Cell Biol. 7, 270-277.
140. Nobes, C. and Hall, A. (1994). Regulation and function of the Rho subfamily of small GTPases. Curr. Opin. Genet. Dev. 4, 77-81.
141. Noda, Y., Takeya, R., Ohno, S., Naito, S., Ito, T. and Sumimoto, H. (2001). Human homologues of the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C. Genes Cells 6, 107-119.
142. Ohta, Y., Hartwig, J. H. and Stossel, T. P. (2006). FilGAP, a Rho- and ROCKregulated GAP for Rac binds filamin A to control actin remodelling. Nat. Cell Biol. 8, 803-814.
143. Olofsson, B. (1999). Rho guanine dissociation inhibitors: pivotal molecules in cellular signalling. Cell. Signal. 11, 545-554.
144. Ooshio, T., Fujita, N., Yamada, A., Sato, T., Kitagawa, Y., Okamoto, R., Nakata, S., Miki, A., Irie, K. and Takai, Y. (2007). Cooperative roles of Par-3 and afadin in the formation of adherens and tight junctions. J. Cell Sci. 120, 2352-2365.
145. Osmani, N., Vitale, N., Borg, J. P. and Etienne-Manneville, S. (2006). Scrib controls Cdc42 localization and activity to promote cell polarization during astrocyte migration. Curr. Biol. 16, 2395-2405.
146. Ossipova, O., Tabler, J., Green, J. B. and Sokol, S. Y. (2007). PAR1 specifies ciliated cells in vertebrate ectoderm downstream of aPKC. Development 134, 4297-4306.
147. Otani, T., Ichii, T., Aono, S. and Takeichi, M. (2006). Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells. J. Cell Biol. 175, 135-146.
148. Ozdamar, B., Bose, R., Barrios-Rodiles, M., Wang, H. R., Zhang, Y. and Wrana, J. L. (2005). Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. Science 307, 1603-1609.
149. Palacios, F., Price, L., Schweitzer, J., Collard, J. G. and D'Souza-Schorey, C. (2001). An essential role for ARF6-regulated membrane traffic in adherens junction turnover and epithelial cell migration. EMBO J. 20, 4973-4986.
150. Palacios, F., Schweitzer, J. K., Boshans, R. L. and D'Souza-Schorey, C. (2002). ARF6-GTP recruits Nm23-H1 to facilitate dynamin-mediated endocytosis during adherens junctions disassembly. Nat. Cell Biol. 4, 929-936.
151. Partanen, J. I., Nieminen, A. I., Mäkelä, T. P. and Klefstrom, J. (2007). Suppression of oncogenic properties of c-Myc by LKB1-controlled epithelial organization. Proc. Natl. Acad. Sci. USA 104, 14694-14699.
152. Peck, J., Douglas, G., 4th, W. u, C. H. and Burbelo, P. D. (2002). Human RhoGAP domain-containing proteins: structure, function and evolutionary relationships. FEBS Lett. 528, 27-34.
153. Pénalva, C. and Mirouse, V. (2012). Tissue-specific function of Patj in regulating the Crumbs complex and epithelial polarity. Development 139, 4549-4554.
154. Peng, C. Y., Manning, L., Albertson, R. and Doe, C. Q. (2000). The tumoursuppressor genes lgl and dlg regulate basal protein targeting in Drosophila neuroblasts. Nature 408, 596-600.
155. Petronczki, M. and Knoblich, J. A. (2001). DmPAR-6 directs epithelial polarity and asymmetric cell division of neuroblasts in Drosophila. Nat. Cell Biol. 3, 43-49.
156. Plant, P. J., Fawcett, J. P., Lin, D. C., Holdorf, A. D., Binns, K., Kulkarni, S. and Pawson, T. (2003). A polarity complex of mPar-6 and atypical PKC binds, phosphorylates and regulates mammalian Lgl. Nat. Cell Biol. 5, 301-308.
157. Poliak, S., Matlis, S., Ullmer, C., Scherer, S. S. and Peles, E. (2002). Distinct claudins and associated PDZ proteins form different autotypic tight junctions in myelinating Schwann cells. J. Cell Biol. 159, 361-372.
158. Qin, Y., Capaldo, C., Gumbiner, B. M. and Macara, I. G. (2005). The mammalian Scribble polarity protein regulates epithelial cell adhesion and migration through E-cadherin. J. Cell Biol. 171, 1061-1071.
159. Qin, Y., Meisen, W. H., Hao, Y. and Macara, I. G. (2010). Tuba, a Cdc42 GEF, is required for polarized spindle orientation during epithelial cyst formation. J. Cell Biol. 189, 661-669.
160. Qiu, R. G., Abo, A. and Steven Martin, G. (2000). A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCzeta signaling and cell transformation. Curr. Biol. 10, 697-707.
161. Ratheesh, A., Gomez, G. A., Priya, R., Verma, S., Kovacs, E. M., Jiang, K., Brown, N. H., Akhmanova, A., Stehbens, S. J. and Yap, A. S. (2012). Centralspindlin and a-catenin regulate Rho signalling at the epithelial zonula adherens. Nat. Cell Biol. 14, 818-828.
162. Richardson, E. C. and Pichaud, F. (2010). Crumbs is required to achieve proper organ size control during Drosophila head development. Development 137, 641-650.
163. Robinson, B. S., Huang, J., Hong, Y. and Moberg, K. H. (2010). Crumbs regulates Salvador/Warts/Hippo signaling in Drosophila via the FERM-domain protein Expanded. Curr. Biol. 20, 582-590.
164. Roh, M. H., Liu, C. J., Laurinec, S. and Margolis, B. (2002a). The carboxyl terminus of zona occludens-3 binds and recruits a mammalian homologue of discs lost to tight junctions. J. Biol. Chem. 277, 27501-27509.
165. Roh, M. H., Makarova, O., Liu, C. J., Shin, K., Lee, S., Laurinec, S., Goyal, M., Wiggins, R. and Margolis, B. (2002b). The Maguk protein, Pals1, functions as an adapter, linking mammalian homologues of Crumbs and Discs Lost. J. Cell Biol. 157, 161-172.
166. Roh, M. H., Fan, S., Liu, C. J. and Margolis, B. (2003). The Crumbs3-Pals1 complex participates in the establishment of polarity in mammalian epithelial cells. J. Cell Sci. 116, 2895-2906.
167. Rossman, K. L., Der, C. J. and Sondek, J. (2005). GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat. Rev. Mol. Cell Biol. 6, 167-180.
168. Sabio, G., Arthur, J. S., Kuma, Y., Peggie, M., Carr, J., Murray-Tait, V., Centeno, F., Goedert, M., Morrice, N. A. and Cuenda, A. (2005). p38gamma regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP. EMBO J. 24, 1134-1145.
169. Samarin, S. N., Ivanov, A. I., Flatau, G., Parkos, C. A. and Nusrat, A. (2007). Rho/Rho-associated kinase-II signaling mediates disassembly of epithelial apical junctions. Mol. Biol. Cell 18, 3429-3439.
170. Schmidt, A. and Hall, A. (2002). Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Dev. 16, 1587-1609.
171. Schmoranzer, J., Fawcett, J. P., Segura, M., Tan, S., Vallee, R. B., Pawson, T. and Gundersen, G. G. (2009). Par3 and dynein associate to regulate local microtubule dynamics and centrosome orientation during migration. Curr. Biol. 19, 1065-1074.
172. Sen, A., Nagy-Zsvér-Vadas, Z. and Krahn, M. P. (2012). Drosophila PATJ supports adherens junction stability by modulating Myosin light chain activity. J. Cell Biol. 199, 685-698.
173. Shin, K., Straight, S. and Margolis, B. (2005). PATJ regulates tight junction formation and polarity in mammalian epithelial cells. J. Cell Biol. 168, 705-711.
174. Shirley, R. L., Walter, N. A., Reilly, M. T., Fehr, C. and Buck, K. J. (2004). Mpdz is a quantitative trait gene for drug withdrawal seizures. Nat. Neurosci. 7, 699-700.
175. Skouloudaki, K., Puetz, M., Simons, M., Courbard, J. R., Boehlke, C., Hartleben, B., Engel, C., Moeller, M. J., Englert, C., Bollig, F. et al. (2009). Scribble participates in Hippo signaling and is required for normal zebrafish pronephros development. Proc. Natl. Acad. Sci. USA 106, 8579-8584.
176. Smith, C. A., Lau, K. M., Rahmani, Z., Dho, S. E., Brothers, G., She, Y. M., Berry, D. M., Bonneil, E., Thibault, P., Schweisguth, F. et al. (2007). aPKCmediated phosphorylation regulates asymmetric membrane localization of the cell fate determinant Numb. EMBO J. 26, 468-480.
177. Sotillos, S., Díaz-Meco, M. T., Caminero, E., Moscat, J. and Campuzano, S. (2004). DaPKC-dependent phosphorylation of Crumbs is required for epithelial cell polarity in Drosophila. J. Cell Biol. 166, 549-557.
178. St Johnston, D. and Ahringer, J. (2010). Cell polarity in eggs and epithelia: parallels and diversity. Cell 141, 757-774.
179. Straight, S. W., Shin, K., Fogg, V. C., Fan, S., Liu, C. J., Roh, M. and Margolis, B. (2004). Loss of PALS1 expression leads to tight junction and polarity defects. Mol. Biol. Cell 15, 1981-1990.
180. Stucke, V. M., Timmerman, E., Vandekerckhove, J., Gevaert, K. and Hall, A. (2007). The MAGUK protein MPP7 binds to the polarity protein hDlg1 and facilitates epithelial tight junction formation. Mol. Biol. Cell 18, 1744-1755.
181. Suzuki, A., Ishiyama, C., Hashiba, K., Shimizu, M., Ebnet, K. and Ohno, S. (2002). aPKC kinase activity is required for the asymmetric differentiation of the premature junctional complex during epithelial cell polarization. J. Cell Sci. 115, 3565-3573.
182. Suzuki, A., Hirata, M., Kamimura, K., Maniwa, R., Yamanaka, T., Mizuno, K., Kishikawa, M., Hirose, H., Amano, Y., Izumi, N. et al. (2004). aPKC acts upstream of PAR-1b in both the establishment and maintenance of mammalian epithelial polarity. Curr. Biol. 14, 1425-1435.
183. Tanentzapf, G. and Tepass, U. (2003). Interactions between the crumbs, lethal giant larvae and bazooka pathways in epithelial polarization. Nat. Cell Biol. 5, 46-52.
184. Tanwar, P. S., Kaneko-Tarui, T., Zhang, L. and Teixeira, J. M. (2012). Altered LKB1/AMPK/TSC1/TSC2/mTOR signaling causes disruption of Sertoli cell polarity and spermatogenesis. Hum. Mol. Genet. 21, 4394-4405.
185. ten Klooster, J. P., Jansen, M., Yuan, J., Oorschot, V., Begthel, H., Di Giacomo, V., Colland, F., de Koning, J., Maurice, M. M., Hornbeck, P. et al. (2009). Mst4 and Ezrin induce brush borders downstream of the Lkb1/Strad/Mo25 polarization complex. Dev. Cell 16, 551-562.
186. Tepass, U., Theres, C. and Knust, E. (1990). crumbs encodes an EGF-like protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia. Cell 61, 787-799.
187. Terry, S. J., Zihni, C., Elbediwy, A., Vitiello, E., Leefa Chong San, I. V., Balda, M. S. and Matter, K. (2011). Spatially restricted activation of RhoA signalling at epithelial junctions by p114RhoGEF drives junction formation and morphogenesis. Nat. Cell Biol. 13, 159-166.
188. Vaezi, A., Bauer, C., Vasioukhin, V. and Fuchs, E. (2002). Actin cable dynamics and Rho/Rock orchestrate a polarized cytoskeletal architecture in the early steps of assembling a stratified epithelium. Dev. Cell 3, 367-381.
189. Van Campenhout, C. A., Eitelhuber, A., Gloeckner, C. J., Giallonardo, P., Gegg, M., Oller, H., Grant, S. G., Krappmann, D., Ueffing, M. and Lickert, H. (2011). Dlg3 trafficking and apical tight junction formation is regulated by nedd4 and nedd4-2 e3 ubiquitin ligases. Dev. Cell 21, 479-491.
190. van den Hurk, J. A., Rashbass, P., Roepman, R., Davis, J., Voesenek, K. E., Arends, M. L., Zonneveld, M. N., van Roekel, M. H., Cameron, K., Rohrschneider, K. et al. (2005). Characterization of the Crumbs homolog 2 (CRβ2) gene and analysis of its role in retinitis pigmentosa and Leber congenital amaurosis. Mol. Vis. 11, 263-273.
191. Varelas, X., Samavarchi-Tehrani, P., Narimatsu, M., Weiss, A., Cockburn, K., Larsen, B. G., Rossant, J. and Wrana, J. L. (2010). The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-b-SMAD pathway. Dev. Cell 19, 831-844.
192. Vitale, N., Patton, W. A., Moss, J., Vaughan, M., Lefkowitz, R. J. and Premont, R. T. (2000). GIT proteins, A novel family of phosphatidylinositol 3, 4, 5-trisphosphate-stimulated GTPase-activating proteins for ARF6. J. Biol. Chem. 275, 13901-13906.
193. Walther, R. F. and Pichaud, F. (2010). Crumbs/DaPKC-dependent apical exclusion of Bazooka promotes photoreceptor polarity remodeling. Curr. Biol. 20, 1065-1074.
194. Wang, Q., Hurd, T. W. and Margolis, B. (2004). Tight junction protein Par6 interacts with an evolutionarily conserved region in the amino terminus of PALS1/stardust. J. Biol. Chem. 279, 30715-30721.
195. Wang, Q., Chen, X. W. and Margolis, B. (2007). PALS1 regulates E-cadherin trafficking in mammalian epithelial cells. Mol. Biol. Cell 18, 874-885.
196. Wang, S., Yang, J., Tsai, A., Kuca, T., Sanny, J., Lee, J., Dong, K., Harden, N. and Krieger, C. (2011). Drosophila adducin regulates Dlg phosphorylation and targeting of Dlg to the synapse and epithelial membrane. Dev. Biol. 357, 392-403.
197. Watkins, J. L., Lewandowski, K. T., Meek, S. E., Storz, P., Toker, A. and Piwnica-Worms, H. (2008). Phosphorylation of the Par-1 polarity kinase by protein kinase D regulates 14-3-3 binding and membrane association. Proc. Natl. Acad. Sci. USA 105, 18378-18383.
198. Wells, C. D., Fawcett, J. P., Traweger, A., Yamanaka, Y., Goudreault, M., Elder, K., Kulkarni, S., Gish, G., Virag, C., Lim, C. et al. (2006). A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells. Cell 125, 535-548.
199. Whiteman, E. L., Liu, C. J., Fearon, E. R. and Margolis, B. (2008). The transcription factor snail represses Crumbs3 expression and disrupts apicobasal polarity complexes. Oncogene 27, 3875-3879.
200. Whiteman, E. L., Fan, S., Harder, J. L., Walton, K. D., Liu, C. J., Soofi, A., Fogg, V. C., Hershenson, M. B., Dressler, G. R., Deutsch, G. H. et al. (2014). Crumbs3 is essential for proper epithelial development and viability. Mol. Cell. Biol. 34, 43-56.
201. Wildenberg, G. A., Dohn, M. R., Carnahan, R. H., Davis, M. A., Lobdell, N. A., Settleman, J. and Reynolds, A. B. (2006). p120-catenin and p190RhoGAP regulate cell-cell adhesion by coordinating antagonism between Rac and Rho. Cell 127, 1027-1039.
202. Winter, J. F., Höpfner, S., Korn, K., Farnung, B. O., Bradshaw, C. R., Marsico, G., Volkmer, M., Habermann, B. and Zerial, M. (2012). Caenorhabditis elegans screen reveals role of PAR-5 in RAB-11-recycling endosome positioning and apicobasal cell polarity. Nat. Cell Biol. 14, 666-676.
203. Wirtz-Peitz, F. and Knoblich, J. A. (2006). Lethal giant larvae take on a life of their own. Trends Cell Biol. 16, 234-241.
204. Wodarz, A., Grawe, F. and Knust, E. (1993). CRUMBS is involved in the control of apical protein targeting during Drosophila epithelial development. Mech. Dev. 44, 175-187.
205. Wodarz, A., Hinz, U., Engelbert, M. and Knust, E. (1995). Expression of crumbs confers apical character on plasma membrane domains of ectodermal epithelia of Drosophila. Cell 82, 67-76.
206. Wodarz, A., Ramrath, A., Grimm, A. and Knust, E. (2000). Drosophila atypical protein kinase C associates with Bazooka and controls polarity of epithelia and neuroblasts. J. Cell Biol. 150, 1361-1374.
207. Woods, D. F., Hough, C., Peel, D., Callaini, G. and Bryant, P. J. (1996). Dlg protein is required for junction structure, cell polarity, and proliferation control in Drosophila epithelia. J. Cell Biol. 134, 1469-1482.
208. Yagi, S., Matsuda, M. and Kiyokawa, E. (2012). Chimaerin suppresses Rac1 activation at the apical membrane to maintain the cyst structure. PLoS ONE 7, e52258.
209. Yamanaka, T., Horikoshi, Y., Suzuki, A., Sugiyama, Y., Kitamura, K., Maniwa, R., Nagai, Y., Yamashita, A., Hirose, T., Ishikawa, H. et al. (2001). PAR-6 regulates aPKC activity in a novel way and mediates cell-cell contactinduced formation of the epithelial junctional complex. Genes Cells 6, 721-731.
210. Yamanaka, T., Horikoshi, Y., Sugiyama, Y., Ishiyama, C., Suzuki, A., Hirose, T., Iwamatsu, A., Shinohara, A. and Ohno, S. (2003). Mammalian Lgl forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity. Curr. Biol. 13, 734-743.
211. Yamanaka, T., Horikoshi, Y., Izumi, N., Suzuki, A., Mizuno, K. and Ohno, S. (2006). Lgl mediates apical domain disassembly by suppressing the PAR-3-aPKC-PAR-6 complex to orient apical membrane polarity. J. Cell Sci. 119, 2107-2118.
212. Yang, Z., Xue, B., Umitsu, M., Ikura, M., Muthuswamy, S. K. and Neel, B. G. (2012). The signaling adaptor GAB1 regulates cell polarity by acting as a PAR protein scaffold. Mol. Cell 47, 469-483.
213. Yates, L. L., Schnatwinkel, C., Hazelwood, L., Chessum, L., Paudyal, A., Hilton, H., Romero, M. R., Wilde, J., Bogani, D., Sanderson, J. et al. (2013). Scribble is required for normal epithelial cell-cell contacts and lumen morphogenesis in the mammalian lung. Dev. Biol. 373, 267-280.
214. Yi, C., Troutman, S., Fera, D., Stemmer-Rachamimov, A., Avila, J. L., Christian, N., Persson, N. L., Shimono, A., Speicher, D. W., Marmorstein, R. et al. (2011). A tight junction-associated Merlin-angiomotin complex mediates Merlin's regulation of mitogenic signaling and tumor suppressive functions. Cancer Cell 19, 527-540.
215. Zhang, H. and Macara, I. G. (2008). The PAR-6 polarity protein regulates dendritic spine morphogenesis through p190 RhoGAP and the Rho GTPase. Dev. Cell 14, 216-226.
216. Zhang, Y., Guo, H., Kwan, H., Wang, J. W., Kosek, J. and Lu, B. (2007). PAR-1 kinase phosphorylates Dlg and regulates its postsynaptic targeting at the Drosophila neuromuscular junction. Neuron 53, 201-215.
217. Zhao, Z. S., Manser, E., Loo, T. H. and Lim, L. (2000). Coupling of PAKinteracting exchange factor PIX to GIT1 promotes focal complex disassembly. Mol. Cell. Biol. 20, 6354-6363.
218. Zhu, J., Shang, Y., Wan, Q., Xia, Y., Chen, J., Du, Q. and Zhang, M. (2014). Phosphorylatiohn-dependent interaction between tumor suppressors Dlg and Lgl. Cell Res. 24, 451-463.
219. Zihni, C., Munro, P. M., Elbediwy, A., Keep, N. H., Terry, S. J., Harris, J., Balda, M. S. and Matter, K. (2014). Dbl3 drives Cdc42 signaling at the apical margin to regulate junction position and apical differentiation. J. Cell Biol. 204, 111-127.