title: Polarity protein complex Scribble/Lgl/Dlg and epithelial cell barriers.
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.
authors: Center for Biomedical Research, Population Council, New York New York, USA.
authors: Wen-Hui
authors: WH
authors: Su
authors: Dolores D
authors: DD
authors: Mruk
authors: Elissa W P
authors: EW
authors: Wong
authors: Wing-Yee
authors: WY
authors: Lui
authors: C Yan
authors: CY
authors: Cheng
mesh_terms: D000818:Animals; D001814:Blood-Testis Barrier / Q000166:cytology / Q000378:metabolism*; D002448:Cell Adhesion; D016764:Cell Polarity; D049109:Cell Proliferation; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D008322:Mammals / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015398:Signal Transduction; D013091:Spermatogenesis; D019108:Tight Junctions / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; C404683:Scrib protein, Drosophila; D025521:Tumor Suppressor Proteins; C070350:dlg1 protein, Drosophila
references: Nature. 2003 May 8;423(6936):173-7
references: 12724779
references: EMBO Rep. 2003 Nov;4(11):1096-102
references: 14578922
references: Genes Dev. 2004 Aug 15;18(16):1909-25
references: 15314019
references: Dev Biol. 1972 Jan;27(1):71-83
references: 4621757
references: Trends Cell Biol. 2001 Dec;11(12):483-6
references: 11719053
references: Nat Rev Mol Cell Biol. 2008 Nov;9(11):846-59
references: 18946474
references: Tissue Cell. 1988;20(5):645-90
references: 3068832
references: Nat Cell Biol. 2000 Jul;2(7):E114
references: 10878817
references: Dev Biol. 1996 Jul 10;177(1):217-25
references: 8660889
references: Structure. 1995 Feb 15;3(2):177-87
references: 7735834
references: Dev Cell. 2004 Jun;6(6):845-54
references: 15177032
references: Int J Oncol. 2004 May;24(5):1257-61
references: 15067349
references: EMBO J. 1997 Jun 16;16(12):3563-71
references: 9218798
references: J Biol Chem. 2007 Mar 30;282(13):9392-9400
references: 17237226
references: EMBO J. 1985 Jun;4(6):1551-7
references: 3928370
references: Curr Biol. 2002 Feb 5;12(3):221-5
references: 11839275
references: Curr Biol. 2005 Feb 8;15(3):276-82
references: 15694314
references: Mol Cell Biol. 2002 Mar;22(6):1778-91
references: 11865057
references: J Cell Sci. 2009 Aug 1;122(Pt 15):2587-96
references: 19625503
references: Am J Pathol. 2010 Jan;176(1):134-45
references: 19959811
references: Nat Rev Mol Cell Biol. 2001 Apr;2(4):285-93
references: 11283726
references: EMBO J. 1996 Jul 15;15(14):3702-12
references: 8758937
references: Trends Cell Biol. 2005 Feb;15(2):76-83
references: 15695094
references: Nat Cell Biol. 2003 Feb;5(2):137-42
references: 12545177
references: Science. 2000 Jul 7;289(5476):113-6
references: 10884224
references: Trends Biochem Sci. 1995 Sep;20(9):350
references: 7482701
references: J Clin Invest. 1999 Mar;103(6):767-72
references: 10079096
references: J Cell Biol. 2005 Dec 19;171(6):1061-71
references: 16344308
references: J Cell Sci. 2001 Jun;114(Pt 12):2265-77
references: 11493666
references: Dev Biol. 2009 Mar 1;327(1):48-61
references: 19103189
references: Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9818-22
references: 7937897
references: J Cell Biol. 1994 Dec;127(5):1361-73
references: 7962095
references: Genes Cells. 2001 Feb;6(2):107-19
references: 11260256
references: Biochim Biophys Acta. 2008 Mar;1778(3):614-30
references: 18005931
references: J Cell Sci. 2006 May 15;119(Pt 10):2107-18
references: 16638806
references: Mol Biol Cell. 2002 Jan;13(1):158-68
references: 11809830
references: Proc Natl Acad Sci U S A. 1937 Sep;23(9):478-84
references: 16577798
references: Biol Rev Camb Philos Soc. 1978 Feb;53(1):123-68
references: 352413
references: Cell. 1991 Aug 9;66(3):451-64
references: 1651169
references: Nat Cell Biol. 2000 Aug;2(8):531-9
references: 10934474
references: Curr Biol. 2003 Apr 29;13(9):734-43
references: 12725730
references: Cell. 2006 May 5;125(3):535-48
references: 16678097
references: J Endocrinol. 2011 Jun;209(3):337-51
references: 21471187
references: Oncogene. 2006 Jul 20;25(31):4276-85
references: 16532034
references: Cell. 2008 Nov 28;135(5):865-78
references: 19041750
references: J Neurosci. 1996 Nov 1;16(21):6839-52
references: 8824323
references: Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9657-62
references: 18621709
references: Mol Cell Biol. 2000 Nov;20(21):8244-53
references: 11027293
references: Dev Biol. 1974 Jul;39(1):23-36
references: 4209528
references: Oncogene. 2005 Jun 23;24(27):4330-9
references: 15806148
references: Oncogene. 2007 Apr 5;26(16):2272-82
references: 17043654
references: Cell. 1987 Jul 17;50(2):215-25
references: 3036370
references: Trends Biochem Sci. 1999 May;24(5):181-5
references: 10322433
references: J Immunol. 2000 Nov 1;165(9):5127-32
references: 11046044
references: Int Rev Cell Mol Biol. 2009;278:309-53
references: 19815182
references: Dev Biol. 1988 Jun;127(2):392-407
references: 3132409
references: J Cell Biol. 1996 Sep;134(6):1469-82
references: 8830775
references: Trends Genet. 2002 Oct;18(10):494-7
references: 12350333
references: Endocrinology. 2001 May;142(5):1865-77
references: 11316752
references: Annu Rev Genet. 2001;35:747-84
references: 11700298
references: Biochemistry. 1996 Nov 5;35(44):13985-94
references: 8909296
references: Dev Biol. 1989 Jul;134(1):222-35
references: 2471660
references: EMBO J. 2005 Mar 23;24(6):1134-45
references: 15729360
references: Dev Cell. 2007 Nov;13(5):609-622
references: 17981131
references: J Cell Biol. 2007 Aug 13;178(4):575-81
references: 17682048
references: EMBO J. 1986 Nov;5(11):2955-61
references: 12222562
references: J Biol Chem. 2002 Mar 8;277(10):8226-34
references: 11756422
references: J Cell Biochem. 2006 Oct 1;99(2):647-64
references: 16791850
references: Curr Biol. 2002 Apr 2;12(7):531-9
references: 11937021
references: Biochem Biophys Res Commun. 2000 Feb 16;268(2):530-4
references: 10679238
references: Development. 1996 Jul;122(7):2283-94
references: 8681808
references: J Cell Biol. 2003 Dec 8;163(5):1089-98
references: 14657233
references: J Cell Sci. 2006 Mar 15;119(Pt 6):979-87
references: 16525119
references: Nat Cell Biol. 2001 Nov;3(11):983-91
references: 11715019
references: FEBS Lett. 2005 Jul 4;579(17):3725-30
references: 15975580
references: EMBO J. 2001 Oct 15;20(20):5578-86
references: 11598001
references: FASEB J. 2008 Jun;22(6):1945-59
references: 18192323
references: Genetics. 1926 May;11(3):249-66
references: 17246453
references: Exp Cell Res. 2011 Feb 15;317(4):413-22
references: 21146521
references: Nature. 2000 Feb 10;403(6770):676-80
references: 10688207
references: Nature. 2003 Mar 20;422(6929):326-30
references: 12629552
references: Exp Cell Res. 2008 Nov 1;314(18):3306-17
references: 18793635
references: J Cell Biol. 1996 Nov;135(4):1125-37
references: 8922391
references: Nature. 2001 Dec 6;414(6864):638-43
references: 11740560
references: Neuron. 1992 Nov;9(5):929-42
references: 1419001
references: Cell Mol Life Sci. 2006 Nov;63(21):2491-505
references: 16927027
references: Curr Opin Cell Biol. 2002 Oct;14(5):546-56
references: 12231348
references: Biochim Biophys Acta. 2000 Oct 2;1493(3):319-24
references: 11018256
references: Endocrinology. 2003 Apr;144(4):1139-42
references: 12639893
references: Nature. 2009 Jun 25;459(7250):1141-5
references: 19553998
references: Mol Vis. 2005 Dec 28;11:1183-99
references: 16402019
references: Cell. 1995 Jul 14;82(1):67-76
references: 7606787
references: Cell. 2005 Dec 2;123(5):903-15
references: 16325583
references: J Cell Sci. 1996 Jun;109 ( Pt 6):1359-68
references: 8799824
references: Genes Cells. 1998 Jun;3(6):347-55
references: 9734781
references: Oncogene. 2010 Sep 23;29(38):5311-21
references: 20622900
references: Trends Cell Biol. 2007 May;17(5):222-9
references: 17442573
references: Genes Dev. 2007 Mar 1;21(5):483-96
references: 17344411
references: J Biol Chem. 2004 Mar 12;279(11):10157-66
references: 14699157
references: Biol Reprod. 2003 Jun;68(6):2189-206
references: 12606349
references: Exp Cell Res. 2010 Oct 15;316(17):2945-60
references: 20682309
references: Genes Dev. 2004 Mar 1;18(5):559-71
references: 15037549
references: J Cell Sci. 2004 Feb 1;117(Pt 4):527-33
references: 14730010
references: Nat Cell Biol. 2010 Jun;12(6):533-42
references: 20453849
references: Genes Dev. 1997 Dec 1;11(23):3242-53
references: 9389655
references: EMBO J. 1987 Jun;6(6):1791-7
references: 16453778
references: Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11399-404
references: 20534521
references: Cell Mol Life Sci. 2001 Dec;58(14):2085-97
references: 11814058
references: Nat Cell Biol. 2000 Jul;2(7):415-22
references: 10878806
references: Cold Spring Harb Perspect Biol. 2010 Feb;2(2):a000125
references: 20182611
references: Science. 1978 Jun 30;200(4349):1448-59
references: 96525
references: J Cell Biol. 2004 Aug 16;166(4):549-57
references: 15302858
references: Nat Cell Biol. 2003 Jan;5(1):46-52
references: 12510193
references: Mol Biol Cell. 2004 Mar;15(3):1324-33
references: 14718572
references: Endocr Rev. 1994 Feb;15(1):102-15
references: 8156935
references: Nat Cell Biol. 2003 Jan;5(1):53-8
references: 12510194
references: J Biol Chem. 2002 Nov 29;277(48):46730-5
references: 12351654
references: Nature. 1996 Jan 25;379(6563):369-74
references: 8552196
references: J Cell Biol. 1994 Dec;127(5):1345-60
references: 7962094
references: Nat Cell Biol. 2000 Aug;2(8):540-7
references: 10934475
references: Endocrinology. 2009 Oct;150(10):4713-23
references: 19608648
references: J Cell Biol. 2005 Sep 12;170(6):895-901
references: 16157700
references: J Cell Biol. 2004 Dec 20;167(6):1137-46
references: 15611336
references: J Cell Biol. 1993 May;121(3):491-502
references: 8486731
references: Mol Biol Cell. 2004 Apr;15(4):1981-90
references: 14718565
references: J Biomed Biotechnol. 2011;2011:868217
references: 21912482
references: Mol Biol Cell. 2007 May;18(5):1744-55
references: 17332497
references: Biochim Biophys Acta. 2009 Apr;1788(4):761-7
references: 19121284
references: Biochim Biophys Acta. 2008 Mar;1778(3):660-9
references: 17854762
references: Proc Natl Acad Sci U S A. 1938 Jun;24(6):236-42
references: 16588224
references: Bioessays. 2004 Sep;26(9):978-92
references: 15351968
references: J Cell Biol. 2010 Jun 28;189(7):1107-15
references: 20584916
references: Biochem J. 2004 May 15;380(Pt 1):19-30
references: 14741046
references: J Cell Biol. 2008 Dec 15;183(6):1129-43
references: 19064670
references: EMBO J. 2000 Nov 1;19(21):5740-51
references: 11060025
references: Cold Spring Harb Perspect Biol. 2009 Dec;1(6):a002899
references: 20457565
references: Oncogene. 2008 Oct 9;27(46):5988-6001
references: 18641685
references: Development. 2007 May;134(9):1799-807
references: 17435047