XB-ART-37624
Mol Biol Cell
2008 Jul 01;197:2752-65. doi: 10.1091/mbc.e08-02-0198.
Show Gene links
Show Anatomy links
Aurora A phosphorylates MCAK to control ran-dependent spindle bipolarity.
Zhang X
,
Ems-McClung SC
,
Walczak CE
.
???displayArticle.abstract???
During mitosis, mitotic centromere-associated kinesin (MCAK) localizes to chromatin/kinetochores, a cytoplasmic pool, and spindle poles. Its localization and activity in the chromatin region are regulated by Aurora B kinase; however, how the cytoplasmic- and pole-localized MCAK are regulated is currently not clear. In this study, we used Xenopus egg extracts to form spindles in the absence of chromatin and centrosomes and found that MCAK localization and activity are tightly regulated by Aurora A. This regulation is important to focus microtubules at aster centers and to facilitate the transition from asters to bipolar spindles. In particular, we found that MCAK colocalized with NuMA and XMAP215 at the center of Ran asters where its activity is regulated by Aurora A-dependent phosphorylation of S196, which contributes to proper pole focusing. In addition, we found that MCAK localization at spindle poles was regulated through another Aurora A phosphorylation site (S719), which positively enhances bipolar spindle formation. This is the first study that clearly defines a role for MCAK at the spindle poles as well as identifies another key Aurora A substrate that contributes to spindle bipolarity.
???displayArticle.pubmedLink??? 18434591
???displayArticle.pmcLink??? PMC2441684
???displayArticle.link??? Mol Biol Cell
???displayArticle.grants??? [+]
Species referenced: Xenopus laevis
Genes referenced: aurka aurkb ckap5 kif2c numa1 ran
References [+] :
Andrews,
Aurora B regulates MCAK at the mitotic centromere.
2004, Pubmed
Andrews, Aurora B regulates MCAK at the mitotic centromere. 2004, Pubmed
Barros, Aurora A activates D-TACC-Msps complexes exclusively at centrosomes to stabilize centrosomal microtubules. 2005, Pubmed , Xenbase
Bischoff, Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1. 1991, Pubmed , Xenbase
Bischoff, Mitotic regulator protein RCC1 is complexed with a nuclear ras-related polypeptide. 1991, Pubmed
Bonaccorsi, Spindle self-organization and cytokinesis during male meiosis in asterless mutants of Drosophila melanogaster. 1998, Pubmed
Bonaccorsi, Spindle assembly in Drosophila neuroblasts and ganglion mother cells. 2000, Pubmed
Brouhard, XMAP215 is a processive microtubule polymerase. 2008, Pubmed , Xenbase
Carazo-Salas, Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation. 1999, Pubmed , Xenbase
Carazo-Salas, Ran-GTP coordinates regulation of microtubule nucleation and dynamics during mitotic-spindle assembly. 2001, Pubmed , Xenbase
Cassimeris, TOGp, the human homolog of XMAP215/Dis1, is required for centrosome integrity, spindle pole organization, and bipolar spindle assembly. 2004, Pubmed
Ciciarello, Spatial control of mitosis by the GTPase Ran. 2007, Pubmed
Coy, Kinesin's tail domain is an inhibitory regulator of the motor domain. 1999, Pubmed
De Mey, Visualization of microtubules in interphase and mitotic plant cells of Haemanthus endosperm with the immuno-gold staining method. 1982, Pubmed
Desai, Kin I kinesins are microtubule-destabilizing enzymes. 1999, Pubmed , Xenbase
Desai, Assays for microtubule-destabilizing kinesins. 2001, Pubmed
Du, A mammalian Partner of inscuteable binds NuMA and regulates mitotic spindle organization. 2001, Pubmed , Xenbase
Du, LGN blocks the ability of NuMA to bind and stabilize microtubules. A mechanism for mitotic spindle assembly regulation. 2002, Pubmed
Ems-McClung, The interplay of the N- and C-terminal domains of MCAK control microtubule depolymerization activity and spindle assembly. 2007, Pubmed , Xenbase
Ems-McClung, Importin alpha/beta and Ran-GTP regulate XCTK2 microtubule binding through a bipartite nuclear localization signal. 2004, Pubmed , Xenbase
Espeut, Phosphorylation relieves autoinhibition of the kinetochore motor Cenp-E. 2008, Pubmed , Xenbase
Gaetz, Dynein/dynactin regulate metaphase spindle length by targeting depolymerizing activities to spindle poles. 2004, Pubmed , Xenbase
Gaglio, NuMA is required for the organization of microtubules into aster-like mitotic arrays. 1995, Pubmed
Gaglio, Opposing motor activities are required for the organization of the mammalian mitotic spindle pole. 1996, Pubmed , Xenbase
Ganem, Efficient mitosis in human cells lacking poleward microtubule flux. 2005, Pubmed
Giet, The Xenopus laevis aurora-related protein kinase pEg2 associates with and phosphorylates the kinesin-related protein XlEg5. 1999, Pubmed , Xenbase
Giet, The Xenopus laevis aurora/Ip11p-related kinase pEg2 participates in the stability of the bipolar mitotic spindle. 2000, Pubmed , Xenbase
Giet, Drosophila Aurora A kinase is required to localize D-TACC to centrosomes and to regulate astral microtubules. 2002, Pubmed , Xenbase
Glover, Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles. 1995, Pubmed
Gordon, Chromosome movement in mitosis requires microtubule anchorage at spindle poles. 2001, Pubmed
Groen, XRHAMM functions in ran-dependent microtubule nucleation and pole formation during anastral spindle assembly. 2004, Pubmed , Xenbase
Gruss, Ran induces spindle assembly by reversing the inhibitory effect of importin alpha on TPX2 activity. 2001, Pubmed , Xenbase
Hackney, Kinesin undergoes a 9 S to 6 S conformational transition. 1992, Pubmed
Heald, Spindle assembly in Xenopus egg extracts: respective roles of centrosomes and microtubule self-organization. 1997, Pubmed , Xenbase
Helenius, The depolymerizing kinesin MCAK uses lattice diffusion to rapidly target microtubule ends. 2006, Pubmed
Hinchcliffe, Requirement of a centrosomal activity for cell cycle progression through G1 into S phase. 2001, Pubmed
Holmfeldt, MAP4 counteracts microtubule catastrophe promotion but not tubulin-sequestering activity in intact cells. 2002, Pubmed
Howard, Microtubule polymerases and depolymerases. 2007, Pubmed , Xenbase
Hunter, The kinesin-related protein MCAK is a microtubule depolymerase that forms an ATP-hydrolyzing complex at microtubule ends. 2003, Pubmed
Kalab, The ran GTPase regulates mitotic spindle assembly. 1999, Pubmed , Xenbase
Karsenti, Respective roles of centrosomes and chromatin in the conversion of microtubule arrays from interphase to metaphase. 1984, Pubmed , Xenbase
Karsenti, The mitotic spindle: a self-made machine. 2001, Pubmed , Xenbase
Khodjakov, Centrosome-independent mitotic spindle formation in vertebrates. 2000, Pubmed
Khodjakov, Minus-end capture of preformed kinetochore fibers contributes to spindle morphogenesis. 2003, Pubmed
Kinoshita, Reconstitution of physiological microtubule dynamics using purified components. 2001, Pubmed , Xenbase
Kline-Smith, Depletion of centromeric MCAK leads to chromosome congression and segregation defects due to improper kinetochore attachments. 2004, Pubmed , Xenbase
Kline-Smith, The microtubule-destabilizing kinesin XKCM1 regulates microtubule dynamic instability in cells. 2002, Pubmed , Xenbase
Koffa, HURP is part of a Ran-dependent complex involved in spindle formation. 2006, Pubmed , Xenbase
Lan, Aurora B phosphorylates centromeric MCAK and regulates its localization and microtubule depolymerization activity. 2004, Pubmed , Xenbase
Lee, Msps/XMAP215 interacts with the centrosomal protein D-TACC to regulate microtubule behaviour. 2001, Pubmed , Xenbase
Liu, Aurora A, mitotic entry, and spindle bipolarity. 2006, Pubmed , Xenbase
Lohka, Induction of nuclear envelope breakdown, chromosome condensation, and spindle formation in cell-free extracts. 1985, Pubmed , Xenbase
Maney, Mitotic centromere-associated kinesin is important for anaphase chromosome segregation. 1998, Pubmed
McKim, Chromosomal control of meiotic cell division. 1995, Pubmed
Merdes, A complex of NuMA and cytoplasmic dynein is essential for mitotic spindle assembly. 1996, Pubmed , Xenbase
Moore, MCAK associates with the tips of polymerizing microtubules. 2005, Pubmed
Moore, The mechanism, function and regulation of depolymerizing kinesins during mitosis. 2004, Pubmed
Murray, Cell cycle extracts. 1991, Pubmed
Murray, Dominoes and clocks: the union of two views of the cell cycle. 1989, Pubmed
Nachury, Importin beta is a mitotic target of the small GTPase Ran in spindle assembly. 2001, Pubmed , Xenbase
Niethammer, Discrete states of a protein interaction network govern interphase and mitotic microtubule dynamics. 2007, Pubmed , Xenbase
Noetzel, A comparison of the ability of XMAP215 and tau to inhibit the microtubule destabilizing activity of XKCM1. 2005, Pubmed , Xenbase
O'Brien, The Xenopus TACC homologue, maskin, functions in mitotic spindle assembly. 2005, Pubmed , Xenbase
Ohba, Self-organization of microtubule asters induced in Xenopus egg extracts by GTP-bound Ran. 1999, Pubmed , Xenbase
Ohi, Nonredundant functions of Kinesin-13s during meiotic spindle assembly. 2007, Pubmed , Xenbase
Ohi, Differentiation of cytoplasmic and meiotic spindle assembly MCAK functions by Aurora B-dependent phosphorylation. 2004, Pubmed , Xenbase
Peset, Function and regulation of Maskin, a TACC family protein, in microtubule growth during mitosis. 2005, Pubmed , Xenbase
Popov, XMAP215 is required for the microtubule-nucleating activity of centrosomes. 2002, Pubmed , Xenbase
Raff, Centrosomes: Central no more? 2001, Pubmed
Resnick, INCENP and Aurora B promote meiotic sister chromatid cohesion through localization of the Shugoshin MEI-S332 in Drosophila. 2006, Pubmed
Ribbeck, A role for NuSAP in linking microtubules to mitotic chromosomes. 2007, Pubmed , Xenbase
Ribbeck, NuSAP, a mitotic RanGTP target that stabilizes and cross-links microtubules. 2006, Pubmed , Xenbase
Roghi, The Xenopus protein kinase pEg2 associates with the centrosome in a cell cycle-dependent manner, binds to the spindle microtubules and is involved in bipolar mitotic spindle assembly. 1998, Pubmed , Xenbase
Sawin, Mitotic spindle organization by a plus-end-directed microtubule motor. 1992, Pubmed , Xenbase
Sawin, Microtubule flux in mitosis is independent of chromosomes, centrosomes, and antiparallel microtubules. 1994, Pubmed , Xenbase
Sawin, Mitotic spindle assembly by two different pathways in vitro. 1991, Pubmed , Xenbase
Schatz, Importin alpha-regulated nucleation of microtubules by TPX2. 2003, Pubmed , Xenbase
Silljé, HURP is a Ran-importin beta-regulated protein that stabilizes kinetochore microtubules in the vicinity of chromosomes. 2006, Pubmed
Steffen, Aster-free spindle poles in insect spermatocytes: evidence for chromosome-induced spindle formation? 1986, Pubmed
Theurkauf, Meiotic spindle assembly in Drosophila females: behavior of nonexchange chromosomes and the effects of mutations in the nod kinesin-like protein. 1992, Pubmed
Tournebize, Control of microtubule dynamics by the antagonistic activities of XMAP215 and XKCM1 in Xenopus egg extracts. 2000, Pubmed , Xenbase
Tsai, Aurora A kinase-coated beads function as microtubule-organizing centers and enhance RanGTP-induced spindle assembly. 2005, Pubmed , Xenbase
Tsai, A Ran signalling pathway mediated by the mitotic kinase Aurora A in spindle assembly. 2003, Pubmed , Xenbase
Walczak, XKCM1: a Xenopus kinesin-related protein that regulates microtubule dynamics during mitotic spindle assembly. 1996, Pubmed , Xenbase
Walczak, A model for the proposed roles of different microtubule-based motor proteins in establishing spindle bipolarity. , Pubmed , Xenbase
Walczak, XCTK2: a kinesin-related protein that promotes mitotic spindle assembly in Xenopus laevis egg extracts. 1997, Pubmed , Xenbase
Wiese, Role of importin-beta in coupling Ran to downstream targets in microtubule assembly. 2001, Pubmed , Xenbase
Wilde, Stimulation of microtubule aster formation and spindle assembly by the small GTPase Ran. 1999, Pubmed , Xenbase
Wilde, Ran stimulates spindle assembly by altering microtubule dynamics and the balance of motor activities. 2001, Pubmed , Xenbase
Wordeman, Identification and partial characterization of mitotic centromere-associated kinesin, a kinesin-related protein that associates with centromeres during mitosis. 1995, Pubmed
Yu, Phosphorylation and stabilization of HURP by Aurora-A: implication of HURP as a transforming target of Aurora-A. 2005, Pubmed
Zhang, Ran-GTP stabilises microtubule asters and inhibits nuclear assembly in Xenopus egg extracts. 1999, Pubmed , Xenbase
Zhang, Aurora B phosphorylates multiple sites on mitotic centromere-associated kinesin to spatially and temporally regulate its function. 2007, Pubmed , Xenbase
de Saint Phalle, Spindle assembly and mitosis without centrosomes in parthenogenetic Sciara embryos. 1998, Pubmed