title: Phospho-regulated interaction between kinesin-6 Klp9p and microtubule bundler Ase1p promotes spindle elongation.
abstract: The spindle midzone-composed of antiparallel microtubules, microtubule-associated proteins (MAPs), and motors-is the structure responsible for microtubule organization and sliding during anaphase B. In general, MAPs and motors stabilize the midzone and motors produce sliding. We show that fission yeast kinesin-6 motor klp9p binds to the microtubule antiparallel bundler ase1p at the midzone at anaphase B onset. This interaction depends upon the phosphorylation states of klp9p and ase1p. The cyclin-dependent kinase cdc2p phosphorylates and its antagonist phosphatase clp1p dephosphorylates klp9p and ase1p to control the position and timing of klp9p-ase1p interaction. Failure of klp9p-ase1p binding leads to decreased spindle elongation velocity. The ase1p-mediated recruitment of klp9p to the midzone accelerates pole separation, as suggested by computer simulation. Our findings indicate that a phosphorylation switch controls the spatial-temporal interactions of motors and MAPs for proper anaphase B, and suggest a mechanism whereby a specific motor-MAP conformation enables efficient microtubule sliding.
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 10104, USA.
authors.forename: Chuanhai
authors.initials: C
authors.lastname: Fu
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Ward
authors.forename: Isabelle
authors.initials: I
authors.lastname: Loiodice
authors.forename: Guilhem
authors.initials: G
authors.lastname: Velve-Casquillas
authors.forename: Francois J
authors.initials: FJ
authors.lastname: Nedelec
authors.forename: Phong T
authors.initials: PT
authors.lastname: Tran
mesh_terms: D000705:Anaphase / Q000502:physiology; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: C502827:Ase1 protein, S pombe; C498823:Cdc13 protein, S pombe; D018797:Cell Cycle Proteins; D019926:Cyclin B; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D029702:Schizosaccharomyces pombe Proteins; D016203:CDC2 Protein Kinase; C469447:cdc2 protein, S pombe; C439269:Clp1 protein, S. pombe; D017027:Protein Tyrosine Phosphatases; D016547:Kinesins
references.citation: Nat Rev Mol Cell Biol. 2008 Jan;9(1):33-46
references.pmid: 18097444
references.citation: J Cell Biol. 1998 Nov 2;143(3):687-94
references.pmid: 9813090
references.citation: EMBO J. 2002 Nov 15;21(22):6015-24
references.pmid: 12426374
references.citation: Nature. 2000 Sep 7;407(6800):41-7
references.pmid: 10993066
references.citation: Curr Biol. 2003 Aug 5;13(15):R589-91
references.pmid: 12906808
references.citation: J Cell Sci. 1998 Jun;111 ( Pt 12):1603-12
references.pmid: 9601091
references.citation: Curr Biol. 1999 Dec 2;9(23):1423-6
references.pmid: 10607565
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6196-201
references.pmid: 16603632
references.citation: Curr Biol. 2004 Aug 10;14(15):1330-40
references.pmid: 15296749
references.citation: Chromosoma. 2000;109(1-2):103-9
references.pmid: 10855500
references.citation: J Cell Biol. 2002 Mar 4;156(5):783-90
references.pmid: 11877456
references.citation: Mol Biol Cell. 2005 Apr;16(4):1756-68
references.pmid: 15689489
references.citation: Yeast. 1998 Jul;14(10):943-51
references.pmid: 9717240
references.citation: Plant Cell Physiol. 2007 Oct;48(10):1509-13
references.pmid: 17855443
references.citation: Mol Cell. 1998 Dec;2(6):877-85
references.pmid: 9885575
references.citation: J Cell Biol. 2000 Oct 2;151(1):15-28
references.pmid: 11018050
references.citation: J Cell Biol. 1992 Jul;118(1):109-20
references.pmid: 1618897
references.citation: J Proteome Res. 2008 Mar;7(3):1088-97
references.pmid: 18257517
references.citation: Cell Div. 2006 Dec 15;1:31
references.pmid: 17173688
references.citation: J Cell Biol. 1995 Feb;128(4):617-24
references.pmid: 7860634
references.citation: J Cell Biol. 2003 Feb 17;160(4):517-28
references.pmid: 12591913
references.citation: Cell. 2007 Jan 26;128(2):357-68
references.pmid: 17254972
references.citation: Curr Biol. 2008 Nov 11;18(21):1713-7
references.pmid: 18976915
references.citation: Nature. 2004 Aug 19;430(7002):908-13
references.pmid: 15282614
references.citation: Curr Biol. 2004 Jul 13;14(13):1181-6
references.pmid: 15242615
references.citation: Curr Biol. 2008 Nov 25;18(22):1748-53
references.pmid: 19026544
references.citation: J Cell Biol. 2006 Jan 30;172(3):363-72
references.pmid: 16431929
references.citation: Mol Biol Cell. 1998 Nov;9(11):3211-25
references.pmid: 9802907
references.citation: Curr Biol. 2002 Apr 16;12(8):610-21
references.pmid: 11967147
references.citation: J Cell Biol. 2008 Aug 11;182(3):421-8
references.pmid: 18678707
references.citation: Mol Biol Cell. 2002 Jun;13(6):1832-45
references.pmid: 12058052
references.citation: Mol Biol Cell. 2005 Mar;16(3):1200-12
references.pmid: 15616192
references.citation: Yeast. 2000 Jan 30;16(2):149-66
references.pmid: 10641037
references.citation: J Cell Sci. 2001 Jul;114(Pt 14):2649-64
references.pmid: 11683392
references.citation: Int Rev Cytol. 2004;241:53-153
references.pmid: 15548419
references.citation: Biochem J. 2005 Jul 15;389(Pt 2):373-81
references.pmid: 15796717
references.citation: J Cell Sci. 2003 Dec 15;116(Pt 24):4891-903
references.pmid: 14625383
references.citation: Mol Biol Cell. 2005 Mar;16(3):1378-95
references.pmid: 15647375
references.citation: EMBO J. 2006 Oct 18;25(20):4897-908
references.pmid: 17024185
references.citation: Dev Cell. 2006 Sep;11(3):423-30
references.pmid: 16950131
references.citation: Mol Biol Cell. 2000 May;11(5):1765-74
references.pmid: 10793150
references.citation: Curr Biol. 2001 Jun 26;11(12):931-40
references.pmid: 11448769
references.citation: Curr Opin Cell Biol. 2008 Feb;20(1):53-63
references.pmid: 18182282
references.citation: Dev Cell. 2004 Nov;7(5):755-62
references.pmid: 15525536
references.citation: Mol Biol Cell. 2001 Dec;12(12):3919-32
references.pmid: 11739790
references.citation: EMBO J. 2004 Aug 18;23(16):3237-48
references.pmid: 15297875
references.citation: Methods. 2004 Jul;33(3):220-5
references.pmid: 15157889
references.citation: J Cell Biol. 1992 Jul;118(1):95-108
references.pmid: 1618910
references.citation: Dev Cell. 2007 Sep;13(3):433-45
references.pmid: 17765685
references.citation: Science. 2005 Mar 18;307(5716):1735-9
references.pmid: 15774750
references.citation: J Cell Biol. 2002 Jun 24;157(7):1175-86
references.pmid: 12082078
references.citation: J Cell Sci. 2002 Mar 1;115(Pt 5):931-40
references.pmid: 11870212
references.citation: J Cell Biol. 2007 Jun 18;177(6):981-93
references.pmid: 17562791
references.citation: Nat Chem Biol. 2006 Sep;2(9):480-5
references.pmid: 16892050
references.citation: J Cell Biol. 1997 Aug 11;138(3):629-41
references.pmid: 9245791
references.citation: Nature. 1990 Oct 11;347(6293):563-6
references.pmid: 2145514
references.citation: Nature. 2003 Apr 17;422(6933):746-52
references.pmid: 12700768
references.citation: Mol Biol Cell. 1996 Oct;7(10):1639-55
references.pmid: 8898367
references.citation: Curr Biol. 2004 Sep 7;14(17):1569-75
references.pmid: 15341744
references.citation: Mol Biol Cell. 2001 Nov;12(11):3476-88
references.pmid: 11694582
references.citation: Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):343-8
references.pmid: 15625105
references.citation: Nat Cell Biol. 2007 Nov;9(11):1294-302
references.pmid: 17922003
references.citation: Trends Cell Biol. 2006 Feb;16(2):88-96
references.pmid: 16406522
references.citation: Nature. 2005 May 5;435(7038):114-8
references.pmid: 15875026
references.citation: Nature. 1992 Mar 5;356(6364):74-6
references.pmid: 1538784
references.citation: J Cell Biol. 2000 Sep 4;150(5):975-88
references.pmid: 10973989
references.citation: Nat Cell Biol. 2006 May;8(5):470-6
references.pmid: 16604065
references.citation: Dev Cell. 2002 Jan;2(1):41-54
references.pmid: 11782313
references.citation: Curr Biol. 2005 Apr 26;15(8):778-86
references.pmid: 15854913