title: Focal adhesion components are essential for mammalian cell cytokinesis.
abstract: The final stages in mammalian cytokinesis are poorly understood. Previously, we reported that the ADP-ribosyltransferase activity of Pseudomonas aeruginosa type III secreted toxin ExoT inhibits late stages of cytokinesis. Given that Crk adaptor proteins are the major substrates of ExoT ADP-ribosyltransferase activity, we tested the involvement of Crk in cytokinesis. We report that the focal adhesion-associated proteins, Crk and paxillin are essential for completion of cytokinesis. When their function is absent, the cytoplasmic bridge fails to resolve and the daughter cells fuse to form a binucleated cell. During cytokinesis, Crk is required for syntaxin-2 recruitment to the midbody, while paxillin is required for both Crk and syntaxin-2 localization to this compartment. Our data demonstrate that the subcellular localization and the activity of RhoA and citron K, which are essential for early stages of cytokinesis, are not dependent on paxillin, Crk or syntaxin-2. These studies reveal a novel role for Crk and paxillin in cytokinesis and suggest that focal adhesion complex, as a unit, may partake in this fundamental cellular process.
authors.affiliation: Department of Medicine, University of California, San Francisco, California, USA.
authors.forename: Sasha H
authors.initials: SH
authors.lastname: Shafikhani
authors.forename: Keith
authors.initials: K
authors.lastname: Mostov
authors.forename: Joanne
authors.initials: J
authors.lastname: Engel
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D048749:Cytokinesis; D022001:Focal Adhesions / Q000201:enzymology / Q000378:metabolism*; D005799:Genes, Dominant; D006367:HeLa Cells; D006801:Humans; D008322:Mammals / Q000378:metabolism*; D051419:Paxillin / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D050737:Proto-Oncogene Proteins c-crk / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D050827:Syntaxin 1 / Q000378:metabolism
chemical_list: C485285:CRK protein, human; D051419:Paxillin; D020033:Protein Isoforms; D050737:Proto-Oncogene Proteins c-crk; D050827:Syntaxin 1; D016392:Proto-Oncogene Proteins pp60(c-src)
references.citation: J Histochem Cytochem. 2003 Apr;51(4):513-21
references.pmid: 12642630
references.citation: Mol Biol Cell. 2008 Apr;19(4):1680-92
references.pmid: 18272786
references.citation: Curr Pharm Des. 2006;12(5):529-48
references.pmid: 16472145
references.citation: Environ Microbiol. 2002 Aug;4(8):482-6
references.pmid: 12153589
references.citation: Mol Biol Cell. 2008 Apr;19(4):1727-38
references.pmid: 18256290
references.citation: J Cell Biol. 2000 Apr 3;149(1):223-36
references.pmid: 10747099
references.citation: Int Rev Cytol. 1993;144:85-127
references.pmid: 8320063
references.citation: J Cell Sci. 2000 Dec;113 Pt 23:4139-40
references.pmid: 11069756
references.citation: Mol Cell Biol. 2002 Mar;22(5):1412-23
references.pmid: 11839808
references.citation: Biotechniques. 1997 Aug;23(2):304-10
references.pmid: 9266088
references.citation: Cell. 2005 Mar 11;120(5):574-6
references.pmid: 15766521
references.citation: Dev Cell. 2003 May;4(5):753-9
references.pmid: 12737809
references.citation: Biochim Biophys Acta. 2004 Jul 5;1692(2-3):63-76
references.pmid: 15246680
references.citation: J Cell Physiol. 2005 Jul;204(1):344-51
references.pmid: 15700267
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15605-10
references.pmid: 17030800
references.citation: Biochem Biophys Res Commun. 1999 Dec 20;266(2):569-74
references.pmid: 10600543
references.citation: Curr Biol. 2004 Sep 21;14(18):1685-93
references.pmid: 15380073
references.citation: Curr Biol. 2000 Oct 19;10(20):R760-70
references.pmid: 11069103
references.citation: J Biol Chem. 2005 Oct 28;280(43):35953-60
references.pmid: 16123042
references.citation: Cell. 2005 Oct 7;123(1):75-87
references.pmid: 16213214
references.citation: Nature. 1998 Jul 30;394(6692):491-4
references.pmid: 9697773
references.citation: Mol Biol Cell. 2002 May;13(5):1449-61
references.pmid: 12006644
references.citation: J Cell Sci. 2005 Oct 15;118(Pt 20):4849-63
references.pmid: 16219691
references.citation: J Biol Chem. 2007 Feb 23;282(8):5327-39
references.pmid: 17189253
references.citation: Oncogene. 2001 Oct 1;20(44):6348-71
references.pmid: 11607838
references.citation: Curr Opin Chem Biol. 2003 Aug;7(4):490-5
references.pmid: 12941424
references.citation: Physiol Rev. 2004 Oct;84(4):1315-39
references.pmid: 15383653
references.citation: Mol Cell Biol. 2002 Feb;22(3):901-15
references.pmid: 11784865
references.citation: Infect Immun. 2004 Jan;72(1):546-58
references.pmid: 14688136
references.citation: Science. 2005 Mar 18;307(5716):1735-9
references.pmid: 15774750
references.citation: Mol Cell Biol. 2000 Dec;20(23):9018-27
references.pmid: 11074000
references.citation: Curr Biol. 2001 May 15;11(10):735-46
references.pmid: 11378383
references.citation: Cell. 1996 Feb 9;84(3):359-69
references.pmid: 8608589
references.citation: J Biol Chem. 1998 May 8;273(19):11709-13
references.pmid: 9565592
references.citation: Mol Cell Biol. 1994 May;14(5):2883-94
references.pmid: 8164650
references.citation: J Cell Physiol. 1998 Dec;177(4):535-52
references.pmid: 10092207
references.citation: Mol Biol Cell. 2002 Jul;13(7):2448-60
references.pmid: 12134082
references.citation: Immunol Lett. 2006 Apr 15;104(1-2):76-82
references.pmid: 16386802
references.citation: Nature. 1997 Jan 30;385(6615):450-4
references.pmid: 9009194
references.citation: Cell. 2008 Mar 7;132(5):832-45
references.pmid: 18329369
references.citation: Cancer Res. 2006 Jul 15;66(14):7326-33
references.pmid: 16849583
references.citation: J Biol Chem. 2003 Aug 29;278(35):32794-800
references.pmid: 12807879
references.citation: Dev Cell. 2005 Dec;9(6):781-90
references.pmid: 16326390
references.citation: Curr Biol. 2004 Sep 21;14(18):R806-18
references.pmid: 15380095