title: A ZO-1/α5β1-integrin complex regulates cytokinesis downstream of PKCε in NCI-H460 cells plated on fibronectin.
abstract: Recently, we demonstrated that integrin adhesion to the extracellular matrix at the cleavage furrow is essential for cytokinesis of adherent cells. Here, we report that tight junction protein ZO-1 (Zonula Occludens-1) is required for successful cytokinesis in NCI-H460 cells plated on fibronectin. This function of ZO-1 involves interaction with the cytoplasmic domain of α5-integrin to facilitate recruitment of active fibronectin-binding integrins to the base of the cleavage furrow. In the absence of ZO-1, or a functional ZO-1/α5β1-integrin complex, proper actin-dependent constriction between daughter cells is impaired and cells fail cytokinesis. Super-resolution microscopy reveals that in ZO-1 depleted cells the furrow becomes delocalized from the matrix. We also show that PKCε-dependent phosphorylation at Serine168 is required for ZO-1 localization to the furrow and successful cell division. Altogether, our results identify a novel regulatory pathway involving the interplay between ZO-1, α5-integrin and PKCε in the late stages of mammalian cell division.
authors: Center for Biotechnology, University of Turku, Turku, Finland.
authors: Saara
authors: S
authors: Hämälistö
authors: Jeroen
authors: J
authors: Pouwels
authors: Nicola
authors: N
authors: de Franceschi
authors: Markku
authors: M
authors: Saari
authors: Ylva
authors: Y
authors: Ivarsson
authors: Pascale
authors: P
authors: Zimmermann
authors: Andreas
authors: A
authors: Brech
authors: Harald
authors: H
authors: Stenmark
authors: Johanna
authors: J
authors: Ivaska
mesh_terms: D002448:Cell Adhesion; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D048749:Cytokinesis; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D008954:Models, Biological; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D011485:Protein Binding; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D015398:Signal Transduction; D062826:Zonula Occludens-1 Protein / Q000378:metabolism*
chemical_list: D005353:Fibronectins; D039081:Integrin alpha5beta1; D019269:Phosphatidylinositol 4,5-Diphosphate; D062826:Zonula Occludens-1 Protein; D051744:Protein Kinase C-epsilon
references: Annu Rev Cell Dev Biol. 1995;11:549-99
references: 8689569
references: Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13613-8
references: 11717427
references: Histopathology. 1994 Mar;24(3):249-56
references: 7515372
references: Am J Pathol. 2005 May;166(5):1541-54
references: 15855653
references: J Biol Chem. 2004 Oct 22;279(43):44785-94
references: 15292177
references: Curr Biol. 2005 Aug 9;15(15):1407-12
references: 16085494
references: Development. 2002 May;129(9):2141-53
references: 11959824
references: J Cell Sci. 2009 Nov 15;122(Pt 22):4009-11
references: 19910492
references: Br J Cancer. 1996 Feb;73(3):327-31
references: 8562338
references: Genes Dev. 2003 Oct 1;17(19):2465-79
references: 14522949
references: EMBO J. 2005 Jul 20;24(14):2556-65
references: 15961997
references: J Biol Chem. 2006 Aug 25;281(34):24671-7
references: 16790439
references: Ann N Y Acad Sci. 2009 May;1165:113-20
references: 19538295
references: FASEB J. 2002 Nov;16(13):1835-7
references: 12354695
references: Cell Mol Life Sci. 2009 Dec;66(24):3951-66
references: 19784548
references: Nature. 2005 Oct 13;437(7061):1043-7
references: 16222300
references: Cell. 1979 Jun;17(2):295-305
references: 455465
references: EMBO J. 2005 Nov 16;24(22):3834-45
references: 16270034
references: Science. 2003 Mar 14;299(5613):1743-7
references: 12637748
references: Microsc Res Tech. 2000 Apr 15;49(2):202-8
references: 10816260
references: Nat Cell Biol. 2008 Aug;10(8):891-901
references: 18604201
references: J Cell Sci. 1993 Feb;104 ( Pt 2):415-25
references: 7685036
references: Mol Biol Cell. 2008 Sep;19(9):3801-11
references: 18596233
references: Curr Opin Cell Biol. 2008 Oct;20(5):576-82
references: 18621126
references: Cell Cycle. 2009 Feb 15;8(4):549-55
references: 19197162
references: Sci Signal. 2009 Jun 30;2(77):ra32
references: 19567915
references: Nat Cell Biol. 2008 Jun;10(6):716-22
references: 18469806
references: Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20338-43
references: 18077377
references: EMBO J. 2002 Jul 15;21(14):3608-19
references: 12110574
references: Clin Cancer Res. 2000 Jan;6(1):96-101
references: 10656437
references: Cell. 1981 Oct;26(1 Pt 1):107-15
references: 6799205
references: Dev Cell. 2008 Sep;15(3):371-385
references: 18804435
references: Biochem J. 2009 Mar 15;418(3):491-506
references: 19228122
references: Nature. 2005 Sep 8;437(7056):275-80
references: 16094321
references: Nat Methods. 2012 Jun 28;9(7):683-9
references: 22743773
references: Mol Biol Cell. 2008 Jun;19(6):2465-75
references: 18353970
references: EMBO J. 2011 Feb 16;30(4):665-78
references: 21240187
references: Curr Biol. 1998 Mar 12;8(6):343-6
references: 9512420
references: EMBO J. 2007 Mar 21;26(6):1487-98
references: 17318179