title: Coupling between microtubule sliding, plus-end growth and spindle length revealed by kinesin-8 depletion.
abstract: Mitotic spindle length control requires coordination between microtubule (MT) dynamics and motor-generated forces. To investigate how MT plus-end polymerization contributes to spindle length in Drosophila embryos, we studied the dynamics of the MT plus-end depolymerase, kinesin-8, and the effects of kinesin-8 inhibition using mutants and antibody microinjection. As expected, kinesin-8 was found to contribute to anaphase A. Furthermore, kinesin-8 depletion caused: (i) excessive polymerization of interpolar (ip) MT plus ends, which "overgrow" to penetrate distal half spindles; (ii) an increase in the poleward ipMT sliding rate that is coupled to MT plus-end polymerization; (iii) premature spindle elongation during metaphase/anaphase A; and (iv) an increase in the anaphase B spindle elongation rate which correlates linearly with the MT sliding rate. This is best explained by a revised "ipMT sliding/minus-end depolymerization" model for spindle length control which incorporates a coupling between ipMT plus end dynamics and the outward ipMT sliding that drives poleward flux and spindle elongation.
authors.affiliation: Department of Molecular and Cell Biology, One Shields Avenue, University of California Davis, Davis, California 95616, USA.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wang
authors.forename: Ingrid
authors.initials: I
authors.lastname: Brust-Mascher
authors.forename: Dhanya
authors.initials: D
authors.lastname: Cheerambathur
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Scholey
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002453:Cell Cycle / Q000502:physiology; D059006:Chromosomes, Insect; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C104939:KLP67A protein, Drosophila; D008869:Microtubule-Associated Proteins; D011993:Recombinant Fusion Proteins; D016547:Kinesins
references.citation: Bioessays. 1989 Jul;11(1):5-9
references.pmid: 2673231
references.citation: Nat Cell Biol. 2006 Sep;8(9):903-5
references.pmid: 16946736
references.citation: Curr Biol. 2004 Jul 13;14(13):1181-6
references.pmid: 15242615
references.citation: J Cell Biol. 2010 Jan 11;188(1):49-68
references.pmid: 20065089
references.citation: J Cell Biol. 2002 Sep 2;158(5):873-84
references.pmid: 12213835
references.citation: Dev Cell. 2008 Feb;14(2):252-62
references.pmid: 18267093
references.citation: J Cell Biol. 1996 Oct;135(2):399-414
references.pmid: 8896597
references.citation: Biochem Soc Trans. 2009 Oct;37(Pt 5):1045-9
references.pmid: 19754449
references.citation: J Vis Exp. 2009 Sep 15;(31):
references.pmid: 19755959
references.citation: J Cell Biol. 2007 Jun 18;177(6):995-1004
references.pmid: 17576796
references.citation: Mol Syst Biol. 2008;4:195
references.pmid: 18463619
references.citation: Cell Cycle. 2010 Mar 15;9(6):1084-90
references.pmid: 20410686
references.citation: Curr Biol. 2004 Jun 8;14(11):R411-2
references.pmid: 15182685
references.citation: Curr Biol. 2010 Feb 23;20(4):374-80
references.pmid: 20153196
references.citation: J Cell Biol. 2008 Sep 22;182(6):1045-54
references.pmid: 18809721
references.citation: Curr Biol. 2007 May 1;17(9):R326-8
references.pmid: 17470346
references.citation: Philos Trans R Soc Lond B Biol Sci. 2005 Mar 29;360(1455):553-68
references.pmid: 15897180
references.citation: Nat Cell Biol. 2006 Sep;8(9):957-62
references.pmid: 16906145
references.citation: Curr Biol. 2009 Sep 15;19(17):R749-61
references.pmid: 19906577
references.citation: J Cell Sci. 2010 Mar 1;123(Pt 5):767-76
references.pmid: 20144994
references.citation: Cell Motil Cytoskeleton. 1998;39(4):257-60
references.pmid: 9556327
references.citation: Curr Biol. 2008 Dec 9;18(23):1860-4
references.pmid: 19062285
references.citation: Curr Biol. 2007 Mar 20;17(6):488-98
references.pmid: 17346968
references.citation: Mol Biol Cell. 2005 Aug;16(8):3896-907
references.pmid: 15958489
references.citation: J Cell Sci. 2004 Jul 15;117(Pt 16):3669-77
references.pmid: 15252134
references.citation: Cell. 2009 Sep 18;138(6):1174-83
references.pmid: 19766569
references.citation: Mol Biol Cell. 2007 Aug;18(8):3094-104
references.pmid: 17553931
references.citation: Nat Cell Biol. 2005 Jan;7(1):42-7
references.pmid: 15592460
references.citation: Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6611-5
references.pmid: 8341676
references.citation: J Cell Biol. 1988 Aug;107(2):623-33
references.pmid: 3047143
references.citation: Nat Rev Mol Cell Biol. 2010 Feb;11(2):91-102
references.pmid: 20068571
references.citation: Mol Biol Cell. 2009 Mar;20(6):1749-62
references.pmid: 19158379
references.citation: Curr Biol. 2007 Jun 19;17(12):R453-4
references.pmid: 17580072
references.citation: J Cell Biol. 1993 Feb;120(4):935-45
references.pmid: 8432733
references.citation: J Cell Biol. 1987 Aug;105(2):875-86
references.pmid: 3305523
references.citation: Curr Biol. 2007 Aug 21;17(16):1373-83
references.pmid: 17702580
references.citation: Annu Rev Cell Dev Biol. 2010;26:21-57
references.pmid: 20604709
references.citation: J Cell Biol. 1999 Jan 11;144(1):125-38
references.pmid: 9885249
references.citation: Nat Cell Biol. 2006 Sep;8(9):913-23
references.pmid: 16906148
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15938-43
references.pmid: 15522967
references.citation: Mol Biol Cell. 2004 Jan;15(1):121-31
references.pmid: 13679514
references.citation: J Cell Biol. 1993 Dec;123(6 Pt 1):1475-89
references.pmid: 8253845
references.citation: Mol Syst Biol. 2009;5:250
references.pmid: 19293830
references.citation: Curr Opin Cell Biol. 2010 Feb;22(1):21-8
references.pmid: 20060701
references.citation: Curr Biol. 2006 Dec 5;16(23):2293-302
references.pmid: 17141610
references.citation: Curr Biol. 2005 Nov 22;15(22):1979-88
references.pmid: 16303556
references.citation: Mol Biol Cell. 2010 Jan 15;21(2):323-33
references.pmid: 19940016
references.citation: Nat Cell Biol. 2000 Dec;2(12):922-30
references.pmid: 11146657
references.citation: Sci Am. 1989 Oct;261(4):48-56
references.pmid: 2781260
references.citation: Mol Biol Cell. 2000 Jan;11(1):241-53
references.pmid: 10637305
references.citation: Mol Biol Cell. 2002 Nov;13(11):3967-75
references.pmid: 12429839