Aurora B Suppresses Microtubule Dynamics and Limits Central Spindle Size by Locally Activating KIF4A

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2013 Aug 14

PMID 23940115

Citations 74

Authors

Ricardo Nunes Bastos

Sapan R Gandhi

Ryan D Baron

Ulrike Gruneberg

Erich A Nigg

Francis A Barr

Affiliations

Soon will be listed here.

Abstract

Anaphase central spindle formation is controlled by the microtubule-stabilizing factor PRC1 and the kinesin KIF4A. We show that an MKlp2-dependent pool of Aurora B at the central spindle, rather than global Aurora B activity, regulates KIF4A accumulation at the central spindle. KIF4A phosphorylation by Aurora B stimulates the maximal microtubule-dependent ATPase activity of KIF4A and promotes its interaction with PRC1. In the presence of phosphorylated KIF4A, microtubules grew more slowly and showed long pauses in growth, resulting in the generation of shorter PRC1-stabilized microtubule overlaps in vitro. Cells expressing only mutant forms of KIF4A lacking the Aurora B phosphorylation site overextended the anaphase central spindle, demonstrating that this regulation is crucial for microtubule length control in vivo. Aurora B therefore ensures that suppression of microtubule dynamic instability by KIF4A is restricted to a specific subset of microtubules and thereby contributes to central spindle size control in anaphase.

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References

Ozlu N, Monigatti F, Renard B, Field C, Steen H, Mitchison T . Binding partner switching on microtubules and aurora-B in the mitosis to cytokinesis transition. Mol Cell Proteomics. 2009; 9(2):336-50. PMC: 2830844. DOI: 10.1074/mcp.M900308-MCP200. View

Gruneberg U, Neef R, Li X, Chan E, Chalamalasetty R, Nigg E . KIF14 and citron kinase act together to promote efficient cytokinesis. J Cell Biol. 2006; 172(3):363-72. PMC: 2063646. DOI: 10.1083/jcb.200511061. View

Elad N, Abramovitch S, Sabanay H, Medalia O . Microtubule organization in the final stages of cytokinesis as revealed by cryo-electron tomography. J Cell Sci. 2010; 124(Pt 2):207-15. DOI: 10.1242/jcs.073486. View

Lee S, McCormick F, Saya H . Mad2 inhibits the mitotic kinesin MKlp2. J Cell Biol. 2010; 191(6):1069-77. PMC: 3002031. DOI: 10.1083/jcb.201003095. View

Nislow C, Lombillo V, Kuriyama R, McIntosh J . A plus-end-directed motor enzyme that moves antiparallel microtubules in vitro localizes to the interzone of mitotic spindles. Nature. 1992; 359(6395):543-7. DOI: 10.1038/359543a0. View

Zhu C, Lau E, Schwarzenbacher R, Bossy-Wetzel E, Jiang W . Spatiotemporal control of spindle midzone formation by PRC1 in human cells. Proc Natl Acad Sci U S A. 2006; 103(16):6196-201. PMC: 1458854. DOI: 10.1073/pnas.0506926103. View

Sekine Y, Okada Y, Noda Y, Kondo S, Aizawa H, Takemura R . A novel microtubule-based motor protein (KIF4) for organelle transports, whose expression is regulated developmentally. J Cell Biol. 1994; 127(1):187-201. PMC: 2120182. DOI: 10.1083/jcb.127.1.187. View

Petronczki M, Glotzer M, Kraut N, Peters J . Polo-like kinase 1 triggers the initiation of cytokinesis in human cells by promoting recruitment of the RhoGEF Ect2 to the central spindle. Dev Cell. 2007; 12(5):713-25. DOI: 10.1016/j.devcel.2007.03.013. View

Santamaria A, Neef R, Eberspacher U, Eis K, Husemann M, Mumberg D . Use of the novel Plk1 inhibitor ZK-thiazolidinone to elucidate functions of Plk1 in early and late stages of mitosis. Mol Biol Cell. 2007; 18(10):4024-36. PMC: 1995727. DOI: 10.1091/mbc.e07-05-0517. View

10.

Gell C, Bormuth V, Brouhard G, Cohen D, Diez S, Friel C . Microtubule dynamics reconstituted in vitro and imaged by single-molecule fluorescence microscopy. Methods Cell Biol. 2010; 95:221-45. DOI: 10.1016/S0091-679X(10)95013-9. View

11.

Pavicic-Kaltenbrunner V, Mishima M, Glotzer M . Cooperative assembly of CYK-4/MgcRacGAP and ZEN-4/MKLP1 to form the centralspindlin complex. Mol Biol Cell. 2007; 18(12):4992-5003. PMC: 2096608. DOI: 10.1091/mbc.e07-05-0468. View

12.

Jiang W, Jimenez G, Wells N, Hope T, Wahl G, Hunter T . PRC1: a human mitotic spindle-associated CDK substrate protein required for cytokinesis. Mol Cell. 1999; 2(6):877-85. DOI: 10.1016/s1097-2765(00)80302-0. View

13.

Kettenbach A, Schweppe D, Faherty B, Pechenick D, Pletnev A, Gerber S . Quantitative phosphoproteomics identifies substrates and functional modules of Aurora and Polo-like kinase activities in mitotic cells. Sci Signal. 2011; 4(179):rs5. PMC: 3808085. DOI: 10.1126/scisignal.2001497. View

14.

Ohi R, Sapra T, Howard J, Mitchison T . Differentiation of cytoplasmic and meiotic spindle assembly MCAK functions by Aurora B-dependent phosphorylation. Mol Biol Cell. 2004; 15(6):2895-906. PMC: 420112. DOI: 10.1091/mbc.e04-02-0082. View

15.

Castoldi M, Popov A . Purification of brain tubulin through two cycles of polymerization-depolymerization in a high-molarity buffer. Protein Expr Purif. 2003; 32(1):83-8. DOI: 10.1016/S1046-5928(03)00218-3. View

16.

Vazquez-Novelle M, Petronczki M . Relocation of the chromosomal passenger complex prevents mitotic checkpoint engagement at anaphase. Curr Biol. 2010; 20(15):1402-7. DOI: 10.1016/j.cub.2010.06.036. View

17.

Zhu C, Zhao J, Bibikova M, Leverson J, Bossy-Wetzel E, Fan J . Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using RNA interference. Mol Biol Cell. 2005; 16(7):3187-99. PMC: 1165403. DOI: 10.1091/mbc.e05-02-0167. View

18.

Fuller B, Lampson M, Foley E, Rosasco-Nitcher S, Le K, Tobelmann P . Midzone activation of aurora B in anaphase produces an intracellular phosphorylation gradient. Nature. 2008; 453(7198):1132-6. PMC: 2724008. DOI: 10.1038/nature06923. View

19.

Kaan H, Hackney D, Kozielski F . The structure of the kinesin-1 motor-tail complex reveals the mechanism of autoinhibition. Science. 2011; 333(6044):883-5. PMC: 3339660. DOI: 10.1126/science.1204824. View

20.

Mishima M, Pavicic V, Gruneberg U, Nigg E, Glotzer M . Cell cycle regulation of central spindle assembly. Nature. 2004; 430(7002):908-13. DOI: 10.1038/nature02767. View