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Polarity Protein Complex Scribble/Lgl/Dlg And Epithelial Cell Barriers

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Biology and Regulation of Blood-Tissue Barriers

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 763))

Abstract

The Scribble polarity complex or module is one of the three polarity modules that regulate cell polarity in multiple epithelia including blood-tissue barriers. This protein complex is composed of Scribble, Lethal giant larvae (Lgl) and Discs large (Dlg), which are well conserved across species from fruitflies and worms to mammals. Originally identified in Drosophila and C. elegans where the Scribble complex was found to work with the Par-based and Crumbs-based polarity modules to regulate apicobasal polarity and asymmetry in cells and tissues during embryogenesis, their mammalian homologs have all been identified in recent years. Components of the Scribble complex are known to regulate multiple cellular functions besides cell polarity, which include cell proliferation, assembly and maintenance of adherens junction (AJ) and tight junction (TJ), and they are also tumor suppressors. Herein, we provide an update on the Scribble polarity complex and how this protein complex modulates cell adhesion with some emphasis on its role in Sertoli cell blood-testis barrier (BTB) function. It should be noted that this is a rapidly developing field, in particular the role of this protein module in blood-tissue barriers, and this short chapter attempts to provide the information necessary for investigators studying reproductive biology and blood-tissue barriers to design future studies. We also include results of recent studies from flies and worms since this information will be helpful in planning experiments for future functional studies in the testis to understand how Scribble-based proteins regulate BTB dynamics and spermatogenesis.

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References

  1. Dym M. Basement membrane regulation of Sertoli cells. Endocr Rev 1994; 15:102–115.

    CAS  PubMed  Google Scholar 

  2. Siu MKY, Cheng CY. Dynamic cross-talk between cells and the extracellular matrix in the testis. BioEssays 2004; 26:978–992.

    Article  CAS  PubMed  Google Scholar 

  3. Meng W, Takeichi M. Adherens junction: molecular architecture and regulation. Cold Spring Harb Perspect Biol 2009; 1;a002899.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Alberts B et al. Molecular Biology of the Cell (Garland Science, New York, 2002).

    Google Scholar 

  5. Nelson WJ, Yeaman C. Protein trafficking in the exocytic pathway of polarized epithelial cells. Trends Cell Biol 2001; 11:483–486.

    Article  CAS  PubMed  Google Scholar 

  6. Assemat E, Bazellieres E, Pallesi-Pocachard E et al. Polarity complex proteins. Biochim Biophys Acta 2008; 1778:614–630.

    Article  CAS  PubMed  Google Scholar 

  7. Goldstein B, Macara IG. The PAR proteins: fundamental players in animal cell polarization. Dev Cell 2007; 13:609–622.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Suzuki A, Ohno S. The PAR-aPKC system: lessons in polarity. J Cell Sci 2006; 119:979–987.

    Article  CAS  PubMed  Google Scholar 

  9. Noda Y et al. 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 2001; 6, 107–119.

    Article  CAS  PubMed  Google Scholar 

  10. Iden S, Collard JG. Crosstalk between small GTPases and polarity proteins in cell polarization. Nature Rev Mol Cell Biol 2008; 9:846–859.

    Article  CAS  Google Scholar 

  11. Joberty G, Petersen C, Gao L et al. The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nat Cell Biol 2000; 2:531–539.

    Article  CAS  PubMed  Google Scholar 

  12. Lin D et al. A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity. Nat Cell Biol 2000; 2:540–547.

    Article  CAS  PubMed  Google Scholar 

  13. Bulgakova NA, Knust E. The Crumbs complex: from epithelial-cell polarity to retinal degeneration. J Cell Sci 2009; 122:2587–2596.

    Article  CAS  PubMed  Google Scholar 

  14. Laprise P. Emerging role for epithelial polarity proteins of the crumbs family as potential tumor suppressors. J Biomed Biotechnol 2011; 868217.

    Google Scholar 

  15. Laprise P et al. Yurt, Coracle, Neurexin IV and the Na(+), K(+)-ATPase form a novel group of epithelial polarity proteins. Nature 2009; 459:1141–1145.

    Article  CAS  PubMed  Google Scholar 

  16. Mathew D et al. Recruitment of scribble to the synaptic scaffolding complex requires GUK-holder, a novel DLG binding protein. Curr Biol 2002; 12:531–539.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bilder D, Li M, Perrimon N. Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. Science 2000; 289:113–116.

    Article  CAS  PubMed  Google Scholar 

  18. Stewart M, Murphy C, Fristrom JW. The recovery and preliminary characterization of X chromosome mutants affecting imaginal discs of Drosophila melanogaster. Dev Biol 1972; 27:71–83.

    Article  CAS  PubMed  Google Scholar 

  19. Murphy C. Cell death and autonomous gene action in lethals affecting imaginal discs in Drosophila melanogaster. Dev Biol 1974; 39:23–36.

    Article  CAS  PubMed  Google Scholar 

  20. Gateff E. Malignant neoplasms of genetic origin in Drosophila melanogaster. Science 1978; 200:1448–1459.

    Article  CAS  PubMed  Google Scholar 

  21. Perrimon, N. The maternal effect of lethal(1)discs-large-1: a recessive oncogene of Drosophila melanogaster. Dev Biol 1988; 127:392–407.

    Article  CAS  PubMed  Google Scholar 

  22. Woods DF, Bryant PJ. The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions. Cell 1991; 66:451–464.

    Article  CAS  PubMed  Google Scholar 

  23. Hough CD, Woods DF, Park S et al. Organizing a functional junctional complex requires specific domains of the Drosophila MAGUK Discs large. Genes Dev 1997; 11:3242–3253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lue RA, Marfatia SM, Branton D et al. Cloning and characterization of hdlg: the human homologue of the Drosophila discs large tumor suppressor binds to protein 4.1. Proc Natl Acad Sci USA 1994; 91:9818–9822.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Stucke VM, Timmerman E, Vandekerckhove J et al. The MAGUK protein MPP7 binds to the polarity protein hDlg1 and facilitates epithelial tight junction formation. Mol Biol Cell 2007; 18:1744–1755.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Karnak D, Lee S, Margolis B. Identification of multiple binding partners for the amino-terminal domain of synapse-associated protein 97. J Biol Chem 2002; 277:46730–46735.

    Article  CAS  PubMed  Google Scholar 

  27. Bohl J, Brimer N, Lyons C et al. The stardust family protein MPP7 forms a tripartite complex with LIN7 and DLG1 that regulates the stability and localization of DLG1 to cell junctions. J Biol Chem 2007; 282:9392–9400.

    Article  CAS  PubMed  Google Scholar 

  28. Lee S, Fan S, Makarova O et al. A novel and conserved protein-protein interaction domain of mammalian Lin-2/CASK binds and recruits SAP97 to the lateral surface of epithelia. Mol Cell Biol 2002; 22:1778–1791.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lue RA, Brandin E, Chan EP et al. Two independent domains of hDlg are sufficient for subcellular targeting: the PDZ1-2 conformational unit and an alternatively spliced domain. J Cell Biol 1996; 135:1125–1137.

    Article  CAS  PubMed  Google Scholar 

  30. Cho KO, Hunt CA, Kennedy MB. The rat brain postsynaptic density fraction contains a homolog of the Drosophila discs-large tumor suppressor protein. Neuron 1992; 9:929–942.

    Article  CAS  PubMed  Google Scholar 

  31. Itoh M, Nagafuchi A, Yonemura S et al. The 220-kD protein colocalizing with cadherins in non-epithelial cells is identical to ZO-1, a tight junction-associated protein in epithelial cells: cDNA cloning and immunoelectron microscopy. J Cell Biol 1993; 121:491–502.

    Article  CAS  PubMed  Google Scholar 

  32. Kennedy MB. Origin of PDZ (DHR, GLGF) domains. Trends Biochem Sci 1995; 20:350.

    Article  CAS  PubMed  Google Scholar 

  33. Bilder D, Perrimon, N. Localization of apical epithelial determinants by the basolateral PDZ protein Scribble. Nature 2000; 403:676–680.

    Article  CAS  PubMed  Google Scholar 

  34. Nakagawa S, Huibregtse JM. Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase. Mol Cell Biol 2000; 20:8244–8253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Apperson ML, Moon IS, Kennedy MB. Characterization of densin-180, a new brain-specific synaptic protein of the O-sialoglycoprotein family. J Neurosci 1996; 16, 6839–6852.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bilder D et al. Collective nomenclature for LAP proteins. Nat Cell Biol 2000; 2:E114.

    Article  CAS  PubMed  Google Scholar 

  37. Legouis R et al. LET-413 is a basolateral protein required for the assembly of adherens junctions in Caenorhabditis elegans. Nat Cell Biol 2000; 2:415–422.

    Article  CAS  PubMed  Google Scholar 

  38. Santoni MJ, Pontarotti P, Birnbaum D et al. The LAP family: a phylogenetic point of view. Trends Genet 2002; 18:494–497.

    Article  CAS  PubMed  Google Scholar 

  39. Legouis R et al. Basolateral targeting by leucine-rich repeat domains in epithelial cells. EMBO Rep 2003; 4:1096–1102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zeitler J, Hsu CP, Dionne H et al. Domains controlling cell polarity and proliferation in the Drosophila tumor suppressor Scribble. J Cell Biol 2004; 167:1137–1146.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Fanning AS, Anderson JM. PDZ domains: fundamental building blocks in the organization of protein complexes at the plasma membrane. J Clin Invest 1999; 103:767–772.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Scharrer B, Hadorn E. The Structure of the Ring-Gland (Corpus Allatum) in Normal and Lethal Larvae of Drosophila Melanogaster. Proc Natl Acad Sci USA 1938; 24:236–242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hadorn E. An Accelerating Effect of Normal “Ring-Glands” on Puparium-Formation in Lethal Larvae of Drosophila Melanogaster. Proc Natl Acad Sci USA 1937; 23:478–484.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Mechler BM, McGinnis W, Gehring WJ. Molecular cloning of lethal(2)giant larvae, a recessive oncogene of Drosophila melanogaster. EMBO J 1985; 4:1551–1557.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lutzelschwab R, Klambt C, Rossa R et al. A protein product of the Drosophila recessive tumor gene, 1 (2) giant g1, potentially has cell adhesion properties. EMBO J 1987; 6:1791–1797.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Jacob L, Opper M, Metzroth B et al. Structure of the 1(2)g1 gene of Drosophila and delimitation of its tumor suppressor domain. Cell 1987; 50:215–225.

    Article  CAS  PubMed  Google Scholar 

  47. Baek KH. Structural and functional conservation of the lgl recessive oncogenes (Review). Int J Oncol 2004; 24:1257–1261.

    CAS  PubMed  Google Scholar 

  48. Klezovitch O, Fernandez TE, Tapscott SJ et al. Loss of cell polarity causes severe brain dysplasia in Lgl1 knockout mice. Genes Dev 2004; 18:559–571.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Sondek J, Bohm A, Lambright DG et al. Crystal structure of a G-protein beta gamma dimer at 2.1A resolution. Nature 1996; 379:369–374.

    Article  CAS  PubMed  Google Scholar 

  50. Ghosh M, Anthony C, Harlos K et al. The refined structure of the quinoprotein methanol dehydrogenase from Methylobacterium extorquens at 1.94 A. Structure 1995; 3:177–187.

    Article  CAS  PubMed  Google Scholar 

  51. Smith TF, Gaitatzes C, Saxena K et al. The WD repeat: a common architecture for diverse functions. Trends Biochem Sci 1999; 24:181–185.

    Article  CAS  PubMed  Google Scholar 

  52. Li D, Roberts R. WD-repeat proteins: structure characteristics, biological function, and their involvement in human diseases. Cell Mol Life Sci 2001; 58:2085–2097.

    Article  CAS  PubMed  Google Scholar 

  53. Garcia-Higuera I et al. Folding of proteins with WD-repeats: comparison of six members of the WD-repeat superfamily to the G protein beta subunit. Biochemistry 1996; 35:13985–13994.

    Article  CAS  PubMed  Google Scholar 

  54. Croze E et al. Receptor for activated C-kinase (RACK-1), a WD motif-containing protein, specifically associates with the human type I IFN receptor. J Immunol 2000; 165:5127–5132.

    Article  CAS  PubMed  Google Scholar 

  55. Dubrovskaya V et al. Distinct domains of hTAFII100 are required for functional interaction with transcription factor TFIIF beta (RAP30) and incorporation into the TFIID complex. EMBO J 1996; 15:3702–3712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Yamamoto T, Horikoshi, M. Defect in cytokinesis of fission yeast induced by mutation in the WD40 repeat motif of a TFIID subunit. Genes Cells 1998; 3:347–355.

    Article  CAS  PubMed  Google Scholar 

  57. Ohtoshi A, Maeda T, Higashi H et al. Human p55(CDC)/Cdc20 associates with cyclin A and is phosphorylated by the cyclin A-Cdk2 complex. Biochem Biophys Res Commun 2000; 268:530–534.

    Article  CAS  PubMed  Google Scholar 

  58. Kallay LM, McNickle A, Brennwald PJ et al. Scribble associates with two polarity proteins, Lgl2 and Vangl2, via distinct molecular domains. J Cell Biochem 2006; 99:647–664.

    Article  CAS  PubMed  Google Scholar 

  59. Delacour D, Jacob R. Apical protein transport. Cell Mol Life Sci 2006; 63:2491–2505.

    Article  CAS  PubMed  Google Scholar 

  60. Siegrist SE, Doe CQ. Microtubule-induced cortical cell polarity. Genes Dev 2007; 21:483–495.

    Article  CAS  PubMed  Google Scholar 

  61. Watanabe T, Noritake J, Kaibuchi, K. Regulation of microtubules in cell migration. Trends Cell Biol 2005; 15:76–83.

    Article  CAS  PubMed  Google Scholar 

  62. Fristrom D. The cellular basis of epithelial morphogenesis. A review. Tissue Cell 1988; 20:645–690.

    Article  CAS  PubMed  Google Scholar 

  63. Green KJ, Getsios S, Troyanovsky S et al. Intercellular junction assembly, dynamics, and homeostasis. Cold Spring Harb Perspect Biol 2010; 2:a000125.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Drees F, Pokutta S, Yamada S et al. Alpha-catenin is a molecular switch that binds E-cadherin-beta-catenin and regulates actin-filament assembly. Cell 2010; 123:903–915.

    Article  CAS  Google Scholar 

  65. le Duc Q et al. Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin II-dependent manner. J Cell Biol 2010; 189:1107–1115.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Yonemura S, Wada Y, Watanabe T et al. alpha-Catenin as a tension transducer that induces adherens junction development. Nat Cell Biol 2010; 12:533–542.

    Article  CAS  PubMed  Google Scholar 

  67. Okada T, You L, Giancotti FG. Shedding light on Merlin’s wizardry. Trends Cell Biol 2007; 17:222–229.

    Article  CAS  PubMed  Google Scholar 

  68. Balda MS, Matter K. Tight junctions and the regulation of gene expression. Biochim Biophys Acta 2009; 1788:761–767.

    Article  CAS  PubMed  Google Scholar 

  69. Braga VM. Cell-cell adhesion and signalling. Curr Opin Cell Biol 2002; 14:546–556.

    Article  CAS  PubMed  Google Scholar 

  70. Harris KP, Tepass U. Cdc42 and Par proteins stabilize dynamic adherens junctions in the Drosophila neuroectoderm through regulation of apical endocytosis. J Cell Biol 2008; 183:1129–1143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Wong EWP, Mruk DD, Lee WM et al. Regulation of blood-testis barrier dynamics by TGF-β3 is a Cdc42-dependent protein trafficking event. Proc Natl Acad Sci USA 2010; 107:11399–11404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Wong EWP, Cheng CY. Polarity proteins and cell-cell interactions in the testis. Int Rev Cell Mol Biol 2009; 278:309–353.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Lui WY, Wong CH, Mruk DD et al. TGF-β3 regulates the blood-testis barrier dynamics via the p38 mitogen activated protein (MAP) kinase pathway: an in vivo study. Endocrinology 2003; 144:1139–1142.

    Article  CAS  PubMed  Google Scholar 

  74. Lui WY, Lee WM, Cheng CY. Transforming growth factor-β3 perturbs the inter-Sertoli tight junction permeability barrier in vitro possibly mediated via its effects on occludin, zonula occludens-1, and claudin-11. Endocrinology 2001; 142:1865–1877.

    Article  CAS  PubMed  Google Scholar 

  75. Xia W, Wong EWP, Mruk DD et al. TGF-β3 and TNFα perturb blood-testis barrier (BTB) dynamics by accelerating the clathrin-mediated endocytosis of integral membrane proteins: A new concept of BTB regulation during spermatogenesis. Dev Biol 2009; 327:48–61.

    Article  CAS  PubMed  Google Scholar 

  76. Yan HHN, Mruk DD, Lee WM et al. Blood-testis barrier dynamics are regulated by testosterone and cytokines via their differential effects on the kinetics of protein endocytosis and recycling in Sertoli cells. FASEB J 2008; 22:1945–1959.

    Article  CAS  PubMed  Google Scholar 

  77. Su L, Mruk DD, Lee WM et al. Differential effects of testosterone and TGF-β3 on endocytic vesicle-mediated protein trafficking events at the blood-testis barrier. Exp Cell Res 2010; 316:2945–2960.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Woods DF, Bryant PJ. Molecular cloning of the lethal(1)discs large-1 oncogene of Drosophila. Dev Biol 1989; 134:222–235.

    Article  CAS  PubMed  Google Scholar 

  79. Woods DF, Hough C, Peel D et al. Dlg protein is required for junction structure, cell polarity, and proliferation control in Drosophila epithelia. J Cell Biol 1996; 134:1469–1482.

    Article  CAS  PubMed  Google Scholar 

  80. Laprise P, Viel A, Rivard N. Human homolog of disc-large is required for adherens junction assembly and differentiation of human intestinal epithelial cells. J Biol Chem 2004; 279:10157–10166.

    Article  CAS  PubMed  Google Scholar 

  81. Laprise P et al. Phosphatidylinositol 3-kinase controls human intestinal epithelial cell differentiation by promoting adherens junction assembly and p38 MAPK activation. J Biol Chem 2002; 277:8226–8234.

    Article  CAS  PubMed  Google Scholar 

  82. Koppen M et al. Cooperative regulation of AJM-1 controls junctional integrity in Caenorhabditis elegans epithelia. Nat Cell Biol 2001; 3:983–991.

    Article  CAS  PubMed  Google Scholar 

  83. McMahon L, Legouis R, Vonesch JL et al. Assembly of C. elegans apical junctions involves positioning and compaction by LET-413 and protein aggregation by the MAGUK protein DLG-1. J Cell Sci 2001; 114:2265–2277.

    CAS  PubMed  Google Scholar 

  84. Tepass U, Tanentzapf G, Ward R et al. Epithelial cell polarity and cell junctions in Drosophila. Annu Rev Genet 2001; 35:747–784.

    Article  CAS  PubMed  Google Scholar 

  85. Navarro C et al. Junctional recruitment of mammalian Scribble relies on E-cadherin engagement. Oncogene 2005; 24:4330–4339.

    Article  CAS  PubMed  Google Scholar 

  86. Dow LE et al. The tumour-suppressor Scribble dictates cell polarity during directed epithelial migration: regulation of Rho GTPase recruitment to the leading edge. Oncogene 2007; 26:2272–2282.

    Article  CAS  PubMed  Google Scholar 

  87. Qin Y, Capaldo C, Gumbiner BM et al. The mammalian Scribble polarity protein regulates epithelial cell adhesion and migration through E-cadherin. J Cell Biol 2005; 171:1061–1071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Zhan L et al. Deregulation of scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma. Cell 2008; 135:865–878.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Chlenski A et al. Organization and expression of the human zo-2 gene (tjp-2) in normal and neoplastic tissues. Biochim Biophys Acta 2000; 1493:319–324.

    Article  CAS  PubMed  Google Scholar 

  90. Glaunsinger BA, Weiss RS, Lee SS et al. Link of the unique oncogenic properties of adenovirus type 9 E4-ORF1 to a select interaction with the candidate tumor suppressor protein ZO-2. EMBO J 2001; 20:5578–5586.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Metais JY, Navarro C, Santoni MJ et al. hScrib interacts with ZO-2 at the cell-cell junctions of epithelial cells. FEBS Lett 2005; 579:3725–3730.

    Article  CAS  PubMed  Google Scholar 

  92. Fanto MMH. Planar polarity from flies to vertebrates. J Cell Sci 2004; 117:527–533.

    Article  CAS  PubMed  Google Scholar 

  93. Montcouquiol M et al. Identification of Vangl2 and Scrb1 as planar polarity genes in mammals. Nature 2003; 423:173–177.

    Article  CAS  PubMed  Google Scholar 

  94. Stark MB, Bridges CB. The Linkage Relations of a Benign Tumor in Drosophila. Genetics 1926; 11:249–266.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Gateff E. The genetics and epigenetics of neoplasms in Drosophila. Biol Rev Camb Philos Soc 1978; 53:123–168.

    Article  CAS  PubMed  Google Scholar 

  96. Klambt C, Schmidt O. Developmental expression and tissue distribution of the lethal (2) giant larvae protein of Drosophila melanogaster. EMBO J 1986; 5:2955–2961.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Strand D, Raska I, Mechler BM. The Drosophila lethal(2)giant larvae tumor suppressor protein is a component of the cytoskeleton. J Cell Biol 1994; 127:1345–1360.

    Article  CAS  PubMed  Google Scholar 

  98. Strand D et al. The Drosophila lethal(2)giant larvae tumor suppressor protein forms homo-oligomers and is associated with nonmuscle myosin II heavy chain. J Cell Biol 1994; 127:1361–1373.

    Article  CAS  PubMed  Google Scholar 

  99. Betschinger J, Mechtler K, Knoblich JA. The Par complex directs asymmetric cell division by phosphorylating the cytoskeletal protein Lgl. Nature 2003; 422:326–330.

    Article  CAS  PubMed  Google Scholar 

  100. Kalmes A, Merdes G, Neumann B et al. A serine-kinase associated with the p127-l(2)gl tumour suppressor of Drosophila may regulate the binding of p127 to nonmuscle myosin II heavy chain and the attachment of p127 to the plasma membrane. J Cell Sci 1996; 109(Pt 6):1359–1368.

    CAS  PubMed  Google Scholar 

  101. Manfruelli P, Arquier N, Hanratty WP et al. The tumor suppressor gene, lethal(2)giant larvae (1(2)g1), is required for cell shape change of epithelial cells during Drosophila development. Development 1996; 122:2283–2294.

    CAS  PubMed  Google Scholar 

  102. Betschinger J, Eisenhaber F, Knoblich JA. Phosphorylation-induced autoinhibition regulates the cytoskeletal protein Lethal (2) giant larvae. Curr Biol 2005; 15:276–282.

    Article  CAS  PubMed  Google Scholar 

  103. Rolls MM, Albertson R, Shih HP et al. Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia. J Cell Biol 2003; 163:1089–1098.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Hutterer A, Betschinger J, Petronczki M et al. Sequential roles of Cdc42, Par-6, aPKC, and Lgl in the establishment of epithelial polarity during Drosophila embryogenesis. Dev Cell 2004; 6:845–854.

    Article  CAS  PubMed  Google Scholar 

  105. Musch A et al. Mammalian homolog of Drosophila tumor suppressor lethal (2) giant larvae interacts with basolateral exocytic machinery in Madin-Darby canine kidney cells. Mol Biol Cell 2002; 13:158–168.

    Article  CAS  PubMed  Google Scholar 

  106. Yamanaka T et al. Mammalian Lgl forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity. Curr Biol 2003; 13:734–743.

    Article  CAS  PubMed  Google Scholar 

  107. Yamanaka T et al. Lgl mediates apical domain disassembly by suppressing the PAR-3-aPKC-PAR-6 complex to orient apical membrane polarity. J Cell Sci 2006; 119:2107–2118.

    Article  CAS  PubMed  Google Scholar 

  108. Bialucha CU, Ferber EC, Pichaud F et al. p32 is a novel mammalian Lgl binding protein that enhances the activity of protein kinase Czeta and regulates cell polarity. J Cell Biol 2007; 178:575–581.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Lemmers C et al. CRB3 binds directly to Par6 and regulates the morphogenesis of the tight junctions in mammalian epithelial cells. Mol Biol Cell 2004; 15:1324–1333.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Sotillos S, Diaz-Meco MT, Caminero E et al. DaPKC-dependent phosphorylation of Crumbs is required for epithelial cell polarity in Drosophila. J Cell Biol 2004; 166:549–557.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Gao L, Joberty G, Macara IG. Assembly of epithelial tight junctions is negatively regulated by Par6. Curr Biol 2002; 12:221–225.

    Article  CAS  PubMed  Google Scholar 

  112. Hurd TW, Gao L, Roh MH et al. Direct interaction of two polarity complexes implicated in epithelial tight junction assembly. Nat Cell Biol 2003; 5:137–142.

    Article  CAS  PubMed  Google Scholar 

  113. Straight SW et al. Loss of PALS1 expression leads to tight junction and polarity defects. Mol Biol Cell 2004; 15:1981–1990.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Tanentzapf G, Tepass U. Interactions between the crumbs, lethal giant larvae and bazooka pathways in epithelial polarization. Nat Cell Biol 2003; 5:46–52.

    Article  CAS  PubMed  Google Scholar 

  115. Bilder D, Schober M, Perrimon N. Integrated activity of PDZ protein complexes regulates epithelial polarity. Nat Cell Biol 2003; 5:53–58.

    Article  CAS  PubMed  Google Scholar 

  116. Tepass U. Crumbs, a component of the apical membrane, is required for zonula adherens formation in primary epithelia of Drosophila. Dev Biol 1996; 177:217–225.

    Article  CAS  PubMed  Google Scholar 

  117. Bachmann A, Schneider M, Theilenberg E et al. Drosophila Stardust is a partner of Crumbs in the control of epithelial cell polarity. Nature 2001; 414:638–643.

    Article  CAS  PubMed  Google Scholar 

  118. Wodarz A, Hinz U, Engelbert M et al. Expression of crumbs confers apical character on plasma membrane domains of ectodermal epithelia of Drosophila. Cell 1995; 82:67–76.

    Article  CAS  PubMed  Google Scholar 

  119. Bilder D. Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors. Genes Dev 2004; 18:1909–1925.

    Article  CAS  PubMed  Google Scholar 

  120. Wells CD et al. A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells. Cell 2006; 125:535–548.

    Article  CAS  PubMed  Google Scholar 

  121. Etienne-Manneville S, Manneville JB, Nicholls S et al. Cdc42 and Par6-PKCzeta regulate the spatially localized association of Dlg1 and APC to control cell polarization. J Cell Biol 2005; 170:895–901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Goedert M, Cuenda A, Craxton M et al. Activation of the novel stress-activated protein kinase SAPK4 by cytokines and cellular stresses is mediated by SKK3 (MKK6); comparison of its substrate specificity with that of other SAP kinases. EMBO J 1997; 16:3563–3571.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Sabio G et al. Stress-and mitogen-induced phosphorylation of the synapse-associated protein SAP90/ PSD-95 by activation of SAPK3/p38gamma and ERK1/ERK2. Biochem J 2004; 380:19–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Sabio G et al. p38gamma regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP. EMBO J 2005; 24:1134–1145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Wu H et al. Intramolecular interactions regulate SAP97 binding to GKAP. EMBO J 2000; 19:5740–5751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Massimi P, Narayan N, Cuenda A et al. Phosphorylation of the discs large tumour suppressor protein controls its membrane localisation and enhances its susceptibility to HPV E6-induced degradation. Oncogene 2006; 25:4276–4285.

    Article  CAS  PubMed  Google Scholar 

  127. Dow LE et al. Loss of human Scribble cooperates with H-Ras to promote cell invasion through deregulation of MAPK signalling. Oncogene 2008; 27:5988–6001.

    Article  CAS  PubMed  Google Scholar 

  128. Nagasaka K et al. The cell polarity regulator hScrib controls ERK activation through a KIM site-dependent interaction. Oncogene 2010; 29:5311–5321.

    Article  CAS  PubMed  Google Scholar 

  129. Massimi P et al. Regulation of the hDlg/hScrib/Hugl-1 tumour suppressor complex. Exp Cell Res 2008; 314:3306–3317.

    Article  CAS  PubMed  Google Scholar 

  130. Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2001; 2:285–293.

    Article  CAS  PubMed  Google Scholar 

  131. Hartsock A, Nelson WJ. Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochim Biophys Acta 2008; 1778:660–669.

    Article  CAS  PubMed  Google Scholar 

  132. Ivanov AI et al. Tumor suppressor scribble regulates assembly of tight junctions in the intestinal epithelium. Am J Pathol 2010; 176:134–145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Nguyen MM, Rivera C, Griep AE. Localization of PDZ domain containing proteins Discs Large-1 and Scribble in the mouse eye. Mol Vis 2005; 11:1183–1199.

    CAS  PubMed  Google Scholar 

  134. Yoshihara K et al. Phosphorylation state regulates the localization of Scribble at adherens junctions and its association with E-cadherin-catenin complexes. Exp Cell Res 2011; 317:413–422.

    Article  CAS  PubMed  Google Scholar 

  135. Iizuka-Kogo A, Ishidao T, Akiyama T et al. Abnormal development of urogenital organs in Dlgh1-deficient mice. Development 2007; 134:1799–1807.

    Article  CAS  PubMed  Google Scholar 

  136. Wong EWP, Mruk DD, Lee WM et al. Par3/Par6 polarity complex coordinates apical ectoplasmic specialization and blood-testis barrier restructuring during spermatogenesis. Proc Natl Acad Sci USA 2008; 105:9657–9662.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Wong EWP, Sun S, Li MWM et al. 14-3-3 protein regulates cell adhesion in the seminiferous epithelium of rat testes. Endocrinology 2009; 150:4713–4723.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Su L, Mruk DD, Lee WM et al. Drug transporters and blood-testis barrier function. J Endocrinol 2011; 209:337–351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Lui WY, Lee WM, Cheng CY. Sertoli-germ cell adherens junction dynamics in the testis are regulated by RhoB GTPase via the ROCK/LIMK signaling pathway. Biol Reprod 2003; 68:2189–2206.

    Article  CAS  PubMed  Google Scholar 

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Su, WH., Mruk, D.D., Wong, E.W.P., Lui, WY., Cheng, C.Y. (2013). Polarity Protein Complex Scribble/Lgl/Dlg And Epithelial Cell Barriers. In: Cheng, C.Y. (eds) Biology and Regulation of Blood-Tissue Barriers. Advances in Experimental Medicine and Biology, vol 763. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4711-5_7

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