XB-ART-55990
Annu Rev Biochem
2016 Jun 02;85:659-83. doi: 10.1146/annurev-biochem-060815-014528.
Show Gene links
Show Anatomy links
Mechanisms of Mitotic Spindle Assembly.
Petry S
.
???displayArticle.abstract???
Life depends on cell proliferation and the accurate segregation of chromosomes, which are mediated by the microtubule (MT)-based mitotic spindle and ∼200 essential MT-associated proteins. Yet, a mechanistic understanding of how the mitotic spindle is assembled and achieves chromosome segregation is still missing. This is mostly due to the density of MTs in the spindle, which presumably precludes their direct observation. Recent insight has been gained into the molecular building plan of the metaphase spindle using bulk and single-molecule measurements combined with computational modeling. MT nucleation was uncovered as a key principle of spindle assembly, and mechanistic details about MT nucleation pathways and their coordination are starting to be revealed. Lastly, advances in studying spindle assembly can be applied to address the molecular mechanisms of how the spindle segregates chromosomes.
???displayArticle.pubmedLink??? 27145846
???displayArticle.pmcLink??? PMC5016079
???displayArticle.link??? Annu Rev Biochem
???displayArticle.grants??? [+]
Species referenced: Xenopus laevis
References [+] :
Akhmanova,
Tracking the ends: a dynamic protein network controls the fate of microtubule tips.
2008, Pubmed
Akhmanova, Tracking the ends: a dynamic protein network controls the fate of microtubule tips. 2008, Pubmed
Albee, Phosphorylation of maskin by Aurora-A is regulated by RanGTP and importin beta. 2006, Pubmed , Xenbase
Alushin, High-resolution microtubule structures reveal the structural transitions in αβ-tubulin upon GTP hydrolysis. 2014, Pubmed
Andersen, Proteomic characterization of the human centrosome by protein correlation profiling. 2003, Pubmed
Arnaoutov, Ran-GTP regulates kinetochore attachment in somatic cells. 2005, Pubmed , Xenbase
Basto, Flies without centrioles. 2006, Pubmed
Bayliss, Structural basis of Aurora-A activation by TPX2 at the mitotic spindle. 2003, Pubmed , Xenbase
Bianconi, An estimation of the number of cells in the human body. 2013, Pubmed
Biggins, Captivating capture: how microtubules attach to kinetochores. 2003, Pubmed
Bird, Building a spindle of the correct length in human cells requires the interaction between TPX2 and Aurora A. 2008, Pubmed
Blower, A Rae1-containing ribonucleoprotein complex is required for mitotic spindle assembly. 2005, Pubmed , Xenbase
Brinkley, Microtubules: a brief historical perspective. 1997, Pubmed
Brouhard, The contribution of αβ-tubulin curvature to microtubule dynamics. 2014, Pubmed
Brown, A mutation in the Schizosaccharomyces pombe rae1 gene causes defects in poly(A)+ RNA export and in the cytoskeleton. 1995, Pubmed
Brown, Xenopus tropicalis egg extracts provide insight into scaling of the mitotic spindle. 2007, Pubmed , Xenbase
Brugués, Nucleation and transport organize microtubules in metaphase spindles. 2012, Pubmed , Xenbase
Bucciarelli, Drosophila Dgt6 interacts with Ndc80, Msps/XMAP215, and gamma-tubulin to promote kinetochore-driven MT formation. 2009, Pubmed
Burbank, A new method reveals microtubule minus ends throughout the meiotic spindle. 2006, Pubmed , Xenbase
Burbank, Slide-and-cluster models for spindle assembly. 2007, Pubmed , Xenbase
Carazo-Salas, Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation. 1999, Pubmed , Xenbase
Caudron, Spatial coordination of spindle assembly by chromosome-mediated signaling gradients. 2005, Pubmed , Xenbase
Chan, Arabidopsis cortical microtubules are initiated along, as well as branching from, existing microtubules. 2009, Pubmed
Cheerambathur, Quantitative analysis of an anaphase B switch: predicted role for a microtubule catastrophe gradient. 2007, Pubmed
Choi, CDK5RAP2 stimulates microtubule nucleation by the gamma-tubulin ring complex. 2010, Pubmed
Clausen, Self-organization of anastral spindles by synergy of dynamic instability, autocatalytic microtubule production, and a spatial signaling gradient. 2007, Pubmed , Xenbase
Cleveland, Centromeres and kinetochores: from epigenetics to mitotic checkpoint signaling. 2003, Pubmed
Dasso, The Ran GTPase: theme and variations. 2002, Pubmed
Desai, Microtubule polymerization dynamics. 1997, Pubmed
Dinarina, Chromatin shapes the mitotic spindle. 2009, Pubmed , Xenbase
Ding, Three-dimensional reconstruction and analysis of mitotic spindles from the yeast, Schizosaccharomyces pombe. 1993, Pubmed
Dobbelaere, A genome-wide RNAi screen to dissect centriole duplication and centrosome maturation in Drosophila. 2008, Pubmed
Dogterom, Microtubule organization in vitro. 2013, Pubmed
Duellberg, Reconstitution of a hierarchical +TIP interaction network controlling microtubule end tracking of dynein. 2014, Pubmed
Dumont, Force and length in the mitotic spindle. 2009, Pubmed
Ems-McClung, Importin alpha/beta and Ran-GTP regulate XCTK2 microtubule binding through a bipartite nuclear localization signal. 2004, Pubmed , Xenbase
Eyers, Regulation of Xenopus Aurora A activation by TPX2. 2004, Pubmed , Xenbase
Fu, Self-assembly and sorting of acentrosomal microtubules by TACC3 facilitate kinetochore capture during the mitotic spindle assembly. 2013, Pubmed
Gadde, Mechanisms and molecules of the mitotic spindle. 2004, Pubmed
Gergely, D-TACC: a novel centrosomal protein required for normal spindle function in the early Drosophila embryo. 2000, Pubmed
Gergely, The ch-TOG/XMAP215 protein is essential for spindle pole organization in human somatic cells. 2003, Pubmed
Giet, Drosophila Aurora A kinase is required to localize D-TACC to centrosomes and to regulate astral microtubules. 2002, Pubmed , Xenbase
Gillingham, The PACT domain, a conserved centrosomal targeting motif in the coiled-coil proteins AKAP450 and pericentrin. 2000, Pubmed
Good, Cytoplasmic volume modulates spindle size during embryogenesis. 2013, Pubmed , Xenbase
Goshima, Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle. 2008, Pubmed
Goshima, Genes required for mitotic spindle assembly in Drosophila S2 cells. 2007, Pubmed
Goshima, Control of mitotic spindle length. 2010, Pubmed
Greenan, Centrosome size sets mitotic spindle length in Caenorhabditis elegans embryos. 2010, Pubmed , Xenbase
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
Halpin, Mitotic spindle assembly around RCC1-coated beads in Xenopus egg extracts. 2011, Pubmed , Xenbase
Hara, An allometric relationship between mitotic spindle width, spindle length, and ploidy in Caenorhabditis elegans embryos. 2013, Pubmed
Haren, NEDD1-dependent recruitment of the gamma-tubulin ring complex to the centrosome is necessary for centriole duplication and spindle assembly. 2006, Pubmed
Hayward, Synergy between multiple microtubule-generating pathways confers robustness to centrosome-driven mitotic spindle formation. 2014, Pubmed
Hazel, Changes in cytoplasmic volume are sufficient to drive spindle scaling. 2013, Pubmed , Xenbase
Heald, Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts. 1996, Pubmed , Xenbase
Heald, Spindle assembly in Xenopus egg extracts: respective roles of centrosomes and microtubule self-organization. 1997, Pubmed , Xenbase
Helmke, TPX2 levels modulate meiotic spindle size and architecture in Xenopus egg extracts. 2014, Pubmed , Xenbase
Hetzer, The Ran GTPase as a marker of chromosome position in spindle formation and nuclear envelope assembly. 2002, Pubmed
Ho, Augmin plays a critical role in organizing the spindle and phragmoplast microtubule arrays in Arabidopsis. 2011, Pubmed
Holy, Dynamic instability of microtubules as an efficient way to search in space. 1994, Pubmed
Honnappa, An EB1-binding motif acts as a microtubule tip localization signal. 2009, Pubmed
Hotta, Characterization of the Arabidopsis augmin complex uncovers its critical function in the assembly of the acentrosomal spindle and phragmoplast microtubule arrays. 2012, Pubmed
Howard, Microtubule polymerases and depolymerases. 2007, Pubmed , Xenbase
Hsia, Reconstitution of the augmin complex provides insights into its architecture and function. 2014, Pubmed , Xenbase
Hughes, A microtubule interactome: complexes with roles in cell cycle and mitosis. 2008, Pubmed
Hutchins, Systematic analysis of human protein complexes identifies chromosome segregation proteins. 2010, Pubmed
Inoué, Cell division and the mitotic spindle. 1981, Pubmed
Inoué, Force generation by microtubule assembly/disassembly in mitosis and related movements. 1995, Pubmed
Inoué, Cell motility by labile association of molecules. The nature of mitotic spindle fibers and their role in chromosome movement. 1967, Pubmed
Janson, Efficient formation of bipolar microtubule bundles requires microtubule-bound gamma-tubulin complexes. 2005, Pubmed
Jeganathan, The Rae1-Nup98 complex prevents aneuploidy by inhibiting securin degradation. 2005, Pubmed
Kalab, The ran GTPase regulates mitotic spindle assembly. 1999, Pubmed , Xenbase
Kalab, Visualization of a Ran-GTP gradient in interphase and mitotic Xenopus egg extracts. 2002, Pubmed , Xenbase
Kaláb, Analysis of a RanGTP-regulated gradient in mitotic somatic cells. 2006, Pubmed , Xenbase
Kamasaki, Augmin-dependent microtubule nucleation at microtubule walls in the spindle. 2013, Pubmed
Kapitein, The bipolar mitotic kinesin Eg5 moves on both microtubules that it crosslinks. 2005, Pubmed , Xenbase
Karsenti, The mitotic spindle: a self-made machine. 2001, Pubmed , Xenbase
Kelly, Chromosomal enrichment and activation of the aurora B pathway are coupled to spatially regulate spindle assembly. 2007, Pubmed , Xenbase
Khodjakov, Minus-end capture of preformed kinetochore fibers contributes to spindle morphogenesis. 2003, Pubmed
Khodjakov, Centrosome-independent mitotic spindle formation in vertebrates. 2000, Pubmed
Khodjakov, The sudden recruitment of gamma-tubulin to the centrosome at the onset of mitosis and its dynamic exchange throughout the cell cycle, do not require microtubules. 1999, Pubmed
Kirschner, Microtubule dynamics. , Pubmed
Kirschner, Beyond self-assembly: from microtubules to morphogenesis. 1986, Pubmed
Koffa, HURP is part of a Ran-dependent complex involved in spindle formation. 2006, Pubmed , Xenbase
Kollman, Ring closure activates yeast γTuRC for species-specific microtubule nucleation. 2015, Pubmed
Kollman, Microtubule nucleating gamma-TuSC assembles structures with 13-fold microtubule-like symmetry. 2010, Pubmed
LaFountain, Kinetochore-driven outgrowth of microtubules is a central contributor to kinetochore fiber maturation in crane-fly spermatocytes. 2014, Pubmed
Lawo, Subdiffraction imaging of centrosomes reveals higher-order organizational features of pericentriolar material. 2012, Pubmed
Lawo, HAUS, the 8-subunit human Augmin complex, regulates centrosome and spindle integrity. 2009, Pubmed
Lecland, The dynamics of microtubule minus ends in the human mitotic spindle. 2014, Pubmed
Levy, Mechanisms of intracellular scaling. 2012, Pubmed , Xenbase
Lin, Targeting of γ-tubulin complexes to microtubule organizing centers: conservation and divergence. 2015, Pubmed
Liu, Augmin triggers microtubule-dependent microtubule nucleation in interphase plant cells. 2014, Pubmed
Liu, Xenopus NEDD1 is required for microtubule organization in Xenopus egg extracts. 2008, Pubmed , Xenbase
Loughlin, A computational model predicts Xenopus meiotic spindle organization. 2010, Pubmed , Xenbase
Loughlin, Katanin contributes to interspecies spindle length scaling in Xenopus. 2011, Pubmed , Xenbase
Lüders, GCP-WD is a gamma-tubulin targeting factor required for centrosomal and chromatin-mediated microtubule nucleation. 2006, Pubmed
Ma, Poleward transport of TPX2 in the mammalian mitotic spindle requires dynein, Eg5, and microtubule flux. 2010, Pubmed
Mack, Analysis of mitotic microtubule-associated proteins using mass spectrometry identifies astrin, a spindle-associated protein. 2001, Pubmed
Mahoney, Making microtubules and mitotic spindles in cells without functional centrosomes. 2006, Pubmed
Maiato, Kinetochore-driven formation of kinetochore fibers contributes to spindle assembly during animal mitosis. 2004, Pubmed
Maresca, Spindle assembly in the absence of a RanGTP gradient requires localized CPC activity. 2009, Pubmed , Xenbase
Maresca, Xnf7 contributes to spindle integrity through its microtubule-bundling activity. 2005, Pubmed , Xenbase
Martinez-Campos, The Drosophila pericentrin-like protein is essential for cilia/flagella function, but appears to be dispensable for mitosis. 2004, Pubmed
Mastronarde, Interpolar spindle microtubules in PTK cells. 1993, Pubmed
Maurer, EB1 accelerates two conformational transitions important for microtubule maturation and dynamics. 2014, Pubmed
McGill, Human chromosomes and centrioles as nucleating sites for the in vitro assembly of microtubules from bovine brain tubulin. 1975, Pubmed
McIntosh, The distribution of spindle microtubules during mitosis in cultured human cells. 1971, Pubmed
McKenney, Activation of cytoplasmic dynein motility by dynactin-cargo adapter complexes. 2014, Pubmed
McKim, Chromosomal control of meiotic cell division. 1995, Pubmed
Mennella, Subdiffraction-resolution fluorescence microscopy reveals a domain of the centrosome critical for pericentriolar material organization. 2012, Pubmed
Merdes, A complex of NuMA and cytoplasmic dynein is essential for mitotic spindle assembly. 1996, Pubmed , Xenbase
Meunier, K-fibre minus ends are stabilized by a RanGTP-dependent mechanism essential for functional spindle assembly. 2011, Pubmed , Xenbase
Mishra, The Nup107-160 complex and gamma-TuRC regulate microtubule polymerization at kinetochores. 2010, Pubmed , Xenbase
Mitchison, Sites of microtubule assembly and disassembly in the mitotic spindle. 1986, Pubmed
Mitchison, Dynamic instability of microtubule growth. , Pubmed
Moritz, Recruitment of the gamma-tubulin ring complex to Drosophila salt-stripped centrosome scaffolds. 1998, Pubmed , Xenbase
Murata, Microtubule-dependent microtubule nucleation based on recruitment of gamma-tubulin in higher plants. 2005, Pubmed
Murphy, GCP5 and GCP6: two new members of the human gamma-tubulin complex. 2001, Pubmed
Nachury, Importin beta is a mitotic target of the small GTPase Ran in spindle assembly. 2001, Pubmed , Xenbase
Nakaoka, An inducible RNA interference system in Physcomitrella patens reveals a dominant role of augmin in phragmoplast microtubule generation. 2012, Pubmed
Nédélec, Self-organisation and forces in the microtubule cytoskeleton. 2003, Pubmed
Needleman, Fast microtubule dynamics in meiotic spindles measured by single molecule imaging: evidence that the spindle environment does not stabilize microtubules. 2010, Pubmed , Xenbase
Neumann, Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes. 2010, Pubmed
Nogales, Structural mechanisms underlying nucleotide-dependent self-assembly of tubulin and its relatives. 2006, Pubmed
Nousiainen, Phosphoproteome analysis of the human mitotic spindle. 2006, Pubmed
Oegema, Characterization of two related Drosophila gamma-tubulin complexes that differ in their ability to nucleate microtubules. 1999, Pubmed , Xenbase
Ohba, Self-organization of microtubule asters induced in Xenopus egg extracts by GTP-bound Ran. 1999, Pubmed , Xenbase
Paul, Computer simulations predict that chromosome movements and rotations accelerate mitotic spindle assembly without compromising accuracy. 2009, Pubmed
Pearson, Measuring nanometer scale gradients in spindle microtubule dynamics using model convolution microscopy. 2006, Pubmed
Petry, Microtubule nucleation at the centrosome and beyond. 2015, Pubmed
Petry, Augmin promotes meiotic spindle formation and bipolarity in Xenopus egg extracts. 2011, Pubmed , Xenbase
Petry, Branching microtubule nucleation in Xenopus egg extracts mediated by augmin and TPX2. 2013, Pubmed , Xenbase
Piehl, Centrosome maturation: measurement of microtubule nucleation throughout the cell cycle by using GFP-tagged EB1. 2004, Pubmed
Reber, XMAP215 activity sets spindle length by controlling the total mass of spindle microtubules. 2013, Pubmed , Xenbase
Rebollo, Contribution of noncentrosomal microtubules to spindle assembly in Drosophila spermatocytes. 2004, Pubmed
Ribbeck, A role for NuSAP in linking microtubules to mitotic chromosomes. 2007, Pubmed , Xenbase
Roberts, Reconstitution of dynein transport to the microtubule plus end by kinesin. 2014, Pubmed
Roll-Mecak, Making more microtubules by severing: a common theme of noncentrosomal microtubule arrays? 2006, Pubmed
Roostalu, Complementary activities of TPX2 and chTOG constitute an efficient importin-regulated microtubule nucleation module. 2015, Pubmed
Salmon, Spindle microtubule dynamics in sea urchin embryos: analysis using a fluorescein-labeled tubulin and measurements of fluorescence redistribution after laser photobleaching. 1984, Pubmed
Sampath, The chromosomal passenger complex is required for chromatin-induced microtubule stabilization and spindle assembly. 2004, Pubmed , Xenbase
Santaguida, The life and miracles of kinetochores. 2009, Pubmed
Sauer, Proteome analysis of the human mitotic spindle. 2005, Pubmed
Sawin, Poleward microtubule flux mitotic spindles assembled in vitro. 1991, Pubmed , Xenbase
Schatz, Importin alpha-regulated nucleation of microtubules by TPX2. 2003, Pubmed , Xenbase
Schlager, In vitro reconstitution of a highly processive recombinant human dynein complex. 2014, Pubmed
Schuh, Self-organization of MTOCs replaces centrosome function during acentrosomal spindle assembly in live mouse oocytes. 2007, Pubmed
Schweizer, The dynamic spindle matrix. 2014, Pubmed
Scrofani, Microtubule nucleation in mitosis by a RanGTP-dependent protein complex. 2015, Pubmed , Xenbase
Snyder, Initiation and growth of microtubules from mitotic centers in lysed mammalian cells. 1975, Pubmed
Subramanian, Building complexity: insights into self-organized assembly of microtubule-based architectures. 2012, Pubmed
Takahashi, Centrosomal proteins CG-NAP and kendrin provide microtubule nucleation sites by anchoring gamma-tubulin ring complex. 2002, Pubmed
Tanenbaum, Cytoplasmic dynein crosslinks and slides anti-parallel microtubules using its two motor domains. 2013, Pubmed
Teixidó-Travesa, The where, when and how of microtubule nucleation - one ring to rule them all. 2012, Pubmed
Teixidó-Travesa, The gammaTuRC revisited: a comparative analysis of interphase and mitotic human gammaTuRC redefines the set of core components and identifies the novel subunit GCP8. 2010, Pubmed , Xenbase
Tirnauer, Microtubule plus-end dynamics in Xenopus egg extract spindles. 2004, Pubmed , Xenbase
Trieselmann, Ran modulates spindle assembly by regulating a subset of TPX2 and Kid activities including Aurora A activation. 2003, Pubmed , Xenbase
Tsai, A Ran signalling pathway mediated by the mitotic kinase Aurora A in spindle assembly. 2003, Pubmed , Xenbase
Tsai, A mitotic lamin B matrix induced by RanGTP required for spindle assembly. 2006, Pubmed , Xenbase
Tulu, Molecular requirements for kinetochore-associated microtubule formation in mammalian cells. 2006, Pubmed
Uchiyama, Proteome analysis of human metaphase chromosomes. 2005, Pubmed
Uehara, The augmin complex plays a critical role in spindle microtubule generation for mitotic progression and cytokinesis in human cells. 2009, Pubmed
Verde, Taxol-induced microtubule asters in mitotic extracts of Xenopus eggs: requirement for phosphorylated factors and cytoplasmic dynein. 1991, Pubmed , Xenbase
Walczak, A model for the proposed roles of different microtubule-based motor proteins in establishing spindle bipolarity. , Pubmed , Xenbase
Welburn, The molecular basis for kinesin functional specificity during mitosis. 2013, Pubmed
Wieczorek, Microtubule-associated proteins control the kinetics of microtubule nucleation. 2015, Pubmed
Wiese, Role of importin-beta in coupling Ran to downstream targets in microtubule assembly. 2001, Pubmed , Xenbase
Wiese, A new function for the gamma-tubulin ring complex as a microtubule minus-end cap. 2000, Pubmed , Xenbase
Wilbur, Mitotic spindle scaling during Xenopus development by kif2a and importin α. 2013, Pubmed , Xenbase
Wilde, Stimulation of microtubule aster formation and spindle assembly by the small GTPase Ran. 1999, Pubmed , Xenbase
Winey, Three-dimensional ultrastructure of Saccharomyces cerevisiae meiotic spindles. 2005, Pubmed
Witt, Origin of kinetochore microtubules in Chinese hamster ovary cells. 1980, Pubmed
Wittmann, TPX2, A novel xenopus MAP involved in spindle pole organization. 2000, Pubmed , Xenbase
Wollman, Efficient chromosome capture requires a bias in the 'search-and-capture' process during mitotic-spindle assembly. 2005, Pubmed
Wong, HURP controls spindle dynamics to promote proper interkinetochore tension and efficient kinetochore capture. 2006, Pubmed
Wühr, Evidence for an upper limit to mitotic spindle length. 2008, Pubmed , Xenbase
Yang, Architectural dynamics of the meiotic spindle revealed by single-fluorophore imaging. 2007, Pubmed , Xenbase
Yokoyama, ISWI is a RanGTP-dependent MAP required for chromosome segregation. 2009, Pubmed , Xenbase
Young, Length-dependent anisotropic scaling of spindle shape. 2014, Pubmed
Zanic, Synergy between XMAP215 and EB1 increases microtubule growth rates to physiological levels. 2013, Pubmed
Zheng, Nucleation of microtubule assembly by a gamma-tubulin-containing ring complex. 1995, Pubmed , Xenbase
Zhu, FAM29A promotes microtubule amplification via recruitment of the NEDD1-gamma-tubulin complex to the mitotic spindle. 2008, Pubmed
Zimmerman, Mitosis-specific anchoring of gamma tubulin complexes by pericentrin controls spindle organization and mitotic entry. 2004, Pubmed , Xenbase