Coupling between microtubule sliding, plus-end growth and spindle length revealed by kinesin-8 depletion.
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.
Wang
Haifeng
H
Department of Molecular and Cell Biology, One Shields Avenue, University of California Davis, Davis, California 95616, USA.
Brust-Mascher
Ingrid
I
Cheerambathur
Dhanya
D
Scholey
Jonathan M
JM
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*
D029721:Drosophila Proteins; C104939:KLP67A protein, Drosophila; D008869:Microtubule-Associated Proteins; D011993:Recombinant Fusion Proteins; D016547:Kinesins
Bioessays. 1989 Jul;11(1):5-9
2673231
Nat Cell Biol. 2006 Sep;8(9):903-5
16946736
Curr Biol. 2004 Jul 13;14(13):1181-6
15242615
J Cell Biol. 2010 Jan 11;188(1):49-68
20065089
J Cell Biol. 2002 Sep 2;158(5):873-84
12213835
Dev Cell. 2008 Feb;14(2):252-62
18267093
J Cell Biol. 1996 Oct;135(2):399-414
8896597
Biochem Soc Trans. 2009 Oct;37(Pt 5):1045-9
19754449
J Vis Exp. 2009 Sep 15;(31):
19755959
J Cell Biol. 2007 Jun 18;177(6):995-1004
17576796
Mol Syst Biol. 2008;4:195
18463619
Cell Cycle. 2010 Mar 15;9(6):1084-90
20410686
Curr Biol. 2004 Jun 8;14(11):R411-2
15182685
Curr Biol. 2010 Feb 23;20(4):374-80
20153196
J Cell Biol. 2008 Sep 22;182(6):1045-54
18809721
Curr Biol. 2007 May 1;17(9):R326-8
17470346
Philos Trans R Soc Lond B Biol Sci. 2005 Mar 29;360(1455):553-68
15897180
Nat Cell Biol. 2006 Sep;8(9):957-62
16906145
Curr Biol. 2009 Sep 15;19(17):R749-61
19906577
J Cell Sci. 2010 Mar 1;123(Pt 5):767-76
20144994
Cell Motil Cytoskeleton. 1998;39(4):257-60
9556327
Curr Biol. 2008 Dec 9;18(23):1860-4
19062285
Curr Biol. 2007 Mar 20;17(6):488-98
17346968
Mol Biol Cell. 2005 Aug;16(8):3896-907
15958489
J Cell Sci. 2004 Jul 15;117(Pt 16):3669-77
15252134
Cell. 2009 Sep 18;138(6):1174-83
19766569
Mol Biol Cell. 2007 Aug;18(8):3094-104
17553931
Nat Cell Biol. 2005 Jan;7(1):42-7
15592460
Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6611-5
8341676
J Cell Biol. 1988 Aug;107(2):623-33
3047143
Nat Rev Mol Cell Biol. 2010 Feb;11(2):91-102
20068571
Mol Biol Cell. 2009 Mar;20(6):1749-62
19158379
Curr Biol. 2007 Jun 19;17(12):R453-4
17580072
J Cell Biol. 1993 Feb;120(4):935-45
8432733
J Cell Biol. 1987 Aug;105(2):875-86
3305523
Curr Biol. 2007 Aug 21;17(16):1373-83
17702580
Annu Rev Cell Dev Biol. 2010;26:21-57
20604709
J Cell Biol. 1999 Jan 11;144(1):125-38
9885249
Nat Cell Biol. 2006 Sep;8(9):913-23
16906148
Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15938-43
15522967
Mol Biol Cell. 2004 Jan;15(1):121-31
13679514
J Cell Biol. 1993 Dec;123(6 Pt 1):1475-89
8253845
Mol Syst Biol. 2009;5:250
19293830
Curr Opin Cell Biol. 2010 Feb;22(1):21-8
20060701
Curr Biol. 2006 Dec 5;16(23):2293-302
17141610
Curr Biol. 2005 Nov 22;15(22):1979-88
16303556
Mol Biol Cell. 2010 Jan 15;21(2):323-33
19940016
Nat Cell Biol. 2000 Dec;2(12):922-30
11146657
Sci Am. 1989 Oct;261(4):48-56
2781260
Mol Biol Cell. 2000 Jan;11(1):241-53
10637305
Mol Biol Cell. 2002 Nov;13(11):3967-75
12429839