Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Nanomedicine Summit 2008

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 19 October 2001:
Vol. 294. no. 5542, pp. 543 - 547
DOI: 10.1126/science.1063488
Prev | Table of Contents | Next

Review

The Mitotic Spindle: A Self-Made Machine

E. Karsenti,12 I. Vernos1

The mitotic spindle is a highly dynamic molecular machine composed of tubulin, motors, and other molecules. It assembles around the chromosomes and distributes the duplicated genome to the daughter cells during mitosis. The biochemical and physical principles that govern the assembly of this machine are still unclear. However, accumulated discoveries indicate that chromosomes play a key role. Apparently, they generate a local cytoplasmic state that supports the nucleation and growth of microtubules. Then soluble and chromosome-associated molecular motors sort them into a bipolar array. The emerging picture is that spindle assembly is governed by a combination of modular principles and that their relative contribution may vary in different cell types and in various organisms.

1 Cell Biology and Biophysics Program, EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
2 Institut Jacques Monod, CNRS/Universités Pierre et Marie Curie (Paris 6) and Denis Diderot (Paris 7), Place Jussieu, Paris, France. E-mail: karsenti{at}embl-heidelberg.de and vernos{at}embl-heidelberg.de

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes.
M. Kwon, S. A. Godinho, N. S. Chandhok, N. J. Ganem, A. Azioune, M. Thery, and D. Pellman (2008)
Genes & Dev. 22, 2189-2203
   Abstract »    Full Text »    PDF »
Aurora A Phosphorylates MCAK to Control Ran-dependent Spindle Bipolarity.
X. Zhang, S. C. Ems-McClung, and C. E. Walczak (2008)
Mol. Biol. Cell 19, 2752-2765
   Abstract »    Full Text »    PDF »
Hice1, a Novel Microtubule-Associated Protein Required for Maintenance of Spindle Integrity and Chromosomal Stability in Human Cells.
G. Wu, Y.-T. Lin, R. Wei, Y. Chen, Z. Shan, and W.-H. Lee (2008)
Mol. Cell. Biol. 28, 3652-3662
   Abstract »    Full Text »    PDF »
Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle.
G. Goshima, M. Mayer, N. Zhang, N. Stuurman, and R. D. Vale (2008)
J. Cell Biol. 181, 421-429
   Abstract »    Full Text »    PDF »
Mob4 plays a role in spindle focusing in Drosophila S2 cells.
M. A. Trammell, N. M. Mahoney, D. A. Agard, and R. D. Vale (2008)
J. Cell Sci. 121, 1284-1292
   Abstract »    Full Text »    PDF »
Spatial Regulation Improves Antiparallel Microtubule Overlap during Mitotic Spindle Assembly.
W. E. Channels, F. J. Nedelec, Y. Zheng, and P. A. Iglesias (2008)
Biophys. J. 94, 2598-2609
   Abstract »    Full Text »    PDF »
Energetics and Geometry of FtsZ Polymers: Nucleated Self-Assembly of Single Protofilaments.
S. Huecas, O. Llorca, J. Boskovic, J. Martin-Benito, J. M. Valpuesta, and J. M. Andreu (2008)
Biophys. J. 94, 1796-1806
   Abstract »    Full Text »    PDF »
Spindle assembly in the absence of chromosomes in mouse oocytes.
J.-W. Yang, Z.-L. Lei, Y.-L. Miao, J.-C. Huang, L.-H. Shi, Y.-C. OuYang, Q.-Y. Sun, and D.-Y. Chen (2007)
Reproduction 134, 731-738
   Abstract »    Full Text »    PDF »
Aurora-A: the maker and breaker of spindle poles.
A. R. Barr and F. Gergely (2007)
J. Cell Sci. 120, 2987-2996
   Abstract »    Full Text »    PDF »
Misregulation of the Kinesin-like Protein Subito Induces Meiotic Spindle Formation in the Absence of Chromosomes and Centrosomes.
J. K. Jang, T. Rahman, V. S. Kober, J. Cesario, and K. S. McKim (2007)
Genetics 177, 267-280
   Abstract »    Full Text »    PDF »
Microtubule Motor Ncd Induces Sliding of Microtubules In Vivo.
A. Oladipo, A. Cowan, and V. Rodionov (2007)
Mol. Biol. Cell 18, 3601-3606
   Abstract »    Full Text »    PDF »
Cooperative mechanisms of mitotic spindle formation.
C. B. O'Connell and A. L. Khodjakov (2007)
J. Cell Sci. 120, 1717-1722
   Abstract »    Full Text »    PDF »
Diazonamide toxins reveal an unexpected function for ornithine {delta}-amino transferase in mitotic cell division.
G. Wang, L. Shang, A. W. G. Burgett, P. G. Harran, and X. Wang (2007)
PNAS 104, 2068-2073
   Abstract »    Full Text »    PDF »
A centriole- and RanGTP-independent spindle assembly pathway in meiosis I of vertebrate oocytes.
J. Dumont, S. Petri, F. Pellegrin, M.-E. Terret, M. T. Bohnsack, P. Rassinier, V. Georget, P. Kalab, O. J. Gruss, and M.-H. Verlhac (2007)
J. Cell Biol. 176, 295-305
   Abstract »    Full Text »    PDF »
The Interplay of the N- and C-Terminal Domains of MCAK Control Microtubule Depolymerization Activity and Spindle Assembly.
S. C. Ems-McClung, K. M. Hertzer, X. Zhang, M. W. Miller, and C. E. Walczak (2007)
Mol. Biol. Cell 18, 282-294
   Abstract »    Full Text »    PDF »
Rae1 interaction with NuMA is required for bipolar spindle formation.
R. W. Wong, G. Blobel, and E. Coutavas (2006)
PNAS 103, 19783-19787
   Abstract »    Full Text »    PDF »
Induction of apoptosis by monastrol, an inhibitor of the mitotic kinesin Eg5, is independent of the spindle checkpoint..
G. M. Chin and R. Herbst (2006)
Mol. Cancer Ther. 5, 2580-2591
   Abstract »    Full Text »    PDF »
Ran at a glance..
J. Joseph (2006)
J. Cell Sci. 119, 3481-3484
   Full Text »    PDF »
The Nup107-160 Nucleoporin Complex Is Required for Correct Bipolar Spindle Assembly.
A. V. Orjalo, A. Arnaoutov, Z. Shen, Y. Boyarchuk, S. G. Zeitlin, B. Fontoura, S. Briggs, M. Dasso, and D. J. Forbes (2006)
Mol. Biol. Cell 17, 3806-3818
   Abstract »    Full Text »    PDF »
Contribution of microtubule growth polarity and flux to spindle assembly and functioning in plant cells..
P. Dhonukshe, N. Vischer, and T. W. J. Gadella Jr (2006)
J. Cell Sci. 119, 3193-3205
   Abstract »    Full Text »    PDF »
Biophysical model of self-organized spindle formation patterns without centrosomes and kinetochores.
S. C. Schaffner and J. V. Jose (2006)
PNAS 103, 11166-11171
   Abstract »    Full Text »    PDF »
Dynein-dependent Motility of Microtubules and Nucleation Sites Supports Polarization of the Tubulin Array in the Fungus Ustilago maydis.
G. Fink and G. Steinberg (2006)
Mol. Biol. Cell 17, 3242-3253
   Abstract »    Full Text »    PDF »
NuSAP, a Mitotic RanGTP Target That Stabilizes and Cross-links Microtubules.
K. Ribbeck, A. C. Groen, R. Santarella, M. T. Bohnsack, T. Raemaekers, T. Kocher, M. Gentzel, D. Gorlich, M. Wilm, G. Carmeliet, et al. (2006)
Mol. Biol. Cell 17, 2646-2660
   Abstract »    Full Text »    PDF »
Aurora B is required for mitotic chromatin-induced phosphorylation of Op18/Stathmin.
B. B. Gadea and J. V. Ruderman (2006)
PNAS 103, 4493-4498
   Abstract »    Full Text »    PDF »
Chromokinesin Xklp1 Contributes to the Regulation of Microtubule Density and Organization during Spindle Assembly.
M. Castoldi and I. Vernos (2006)
Mol. Biol. Cell 17, 1451-1460
   Abstract »    Full Text »    PDF »
Molecules into Cells: Specifying Spatial Architecture.
F. M. Harold (2005)
Microbiol. Mol. Biol. Rev. 69, 544-564
   Abstract »    Full Text »    PDF »
Cytoskeleton and cell cycle control during meiotic maturation of the mouse oocyte: integrating time and space.
S. Brunet and B. Maro (2005)
Reproduction 130, 801-811
   Abstract »    Full Text »    PDF »
The Chromokinesin Kid Is Required for Maintenance of Proper Metaphase Spindle Size.
N. Tokai-Nishizumi, M. Ohsugi, E. Suzuki, and T. Yamamoto (2005)
Mol. Biol. Cell 16, 5455-5463
   Abstract »    Full Text »    PDF »
Mechanisms for focusing mitotic spindle poles by minus end-directed motor proteins.
G. Goshima, F. Nedelec, and R. D. Vale (2005)
J. Cell Biol. 171, 229-240
   Abstract »    Full Text »    PDF »
APC and EB1 Function Together in Mitosis to Regulate Spindle Dynamics and Chromosome Alignment.
R. A. Green, R. Wollman, and K. B. Kaplan (2005)
Mol. Biol. Cell 16, 4609-4622
   Abstract »    Full Text »    PDF »
The Kinesinlike Protein Subito Contributes to Central Spindle Assembly and Organization of the Meiotic Spindle in Drosophila Oocytes.
J. K. Jang, T. Rahman, and K. S. McKim (2005)
Mol. Biol. Cell 16, 4684-4694
   Abstract »    Full Text »    PDF »
Aurora A phosphorylation of TACC3/maskin is required for centrosome-dependent microtubule assembly in mitosis.
K. Kinoshita, T. L. Noetzel, L. Pelletier, K. Mechtler, D. N. Drechsel, A. Schwager, M. Lee, J. W. Raff, and A. A. Hyman (2005)
J. Cell Biol. 170, 1047-1055
   Abstract »    Full Text »    PDF »
Function and regulation of Maskin, a TACC family protein, in microtubule growth during mitosis.
I. Peset, J. Seiler, T. Sardon, L. A. Bejarano, S. Rybina, and I. Vernos (2005)
J. Cell Biol. 170, 1057-1066
   Abstract »    Full Text »    PDF »
Spatial Coordination of Spindle Assembly by Chromosome-Mediated Signaling Gradients.
M. Caudron, G. Bunt, P. Bastiaens, and E. Karsenti (2005)
Science 309, 1373-1376
   Abstract »    Full Text »    PDF »
ASAP, a human microtubule-associated protein required for bipolar spindle assembly and cytokinesis.
J.-M. Saffin, M. Venoux, C. Prigent, J. Espeut, F. Poulat, D. Giorgi, A. Abrieu, and S. Rouquier (2005)
PNAS 102, 11302-11307
   Abstract »    Full Text »    PDF »
Spindle Pole Organization in Drosophila S2 Cells by Dynein, Abnormal Spindle Protein (Asp), and KLP10A.
S. Morales-Mulia and J. M. Scholey (2005)
Mol. Biol. Cell 16, 3176-3186
   Abstract »    Full Text »    PDF »
Roles of Polymerization Dynamics, Opposed Motors, and a Tensile Element in Governing the Length of Xenopus Extract Meiotic Spindles.
T. J. Mitchison, P. Maddox, J. Gaetz, A. Groen, M. Shirasu, A. Desai, E. D. Salmon, and T. M. Kapoor (2005)
Mol. Biol. Cell 16, 3064-3076
   Abstract »    Full Text »    PDF »
The Xenopus TACC Homologue, Maskin, Functions in Mitotic Spindle Assembly.
L. L. O'Brien, A. J. Albee, L. Liu, W. Tao, P. Dobrzyn, S. B. Lizarraga, and C. Wiese (2005)
Mol. Biol. Cell 16, 2836-2847
   Abstract »    Full Text »    PDF »
Assembly pathway of the anastral Drosophila oocyte meiosis I spindle.
H. N. Skold, D. J. Komma, and S. A. Endow (2005)
J. Cell Sci. 118, 1745-1755
   Abstract »    Full Text »    PDF »
Monastrol Inhibition of the Mitotic Kinesin Eg5.
J. C. Cochran, J. E. Gatial III, T. M. Kapoor, and S. P. Gilbert (2005)
J. Biol. Chem. 280, 12658-12667
   Abstract »    Full Text »    PDF »
Aurora Kinase Inhibitor ZM447439 Blocks Chromosome-induced Spindle Assembly, the Completion of Chromosome Condensation, and the Establishment of the Spindle Integrity Checkpoint in Xenopus Egg Extracts.
B. B. Gadea and J. V. Ruderman (2005)
Mol. Biol. Cell 16, 1305-1318
   Abstract »    Full Text »    PDF »
Centrosome fragments and microtubules are transported asymmetrically away from division plane in anaphase.
N. M. Rusan and P. Wadsworth (2005)
J. Cell Biol. 168, 21-28
   Abstract »    Full Text »    PDF »
Kinetochore-driven formation of kinetochore fibers contributes to spindle assembly during animal mitosis.
H. Maiato, C. L. Rieder, and A. Khodjakov (2004)
J. Cell Biol. 167, 831-840
   Abstract »    Full Text »    PDF »
Characterization of the TPX2 Domains Involved in Microtubule Nucleation and Spindle Assembly in Xenopus Egg Extracts.
S. Brunet, T. Sardon, T. Zimmerman, T. Wittmann, R. Pepperkok, E. Karsenti, and I. Vernos (2004)
Mol. Biol. Cell 15, 5318-5328
   Abstract »    Full Text »    PDF »
Bipolarization and Poleward Flux Correlate during Xenopus Extract Spindle Assembly.
T.J. Mitchison, P. Maddox, A. Groen, L. Cameron, Z. Perlman, R. Ohi, A. Desai, E.D. Salmon, and T.M. Kapoor (2004)
Mol. Biol. Cell 15, 5603-5615
   Abstract »    Full Text »    PDF »
In Vivo Measurement of Microtubule Dynamics Using Stable Isotope Labeling with Heavy Water: EFFECT OF TAXANES.
P. Fanara, S. Turner, R. Busch, S. Killion, M. Awada, H. Turner, A. Mahsut, K. L. LaPrade, J. M. Stark, and M. K. Hellerstein (2004)
J. Biol. Chem. 279, 49940-49947
   Abstract »    Full Text »    PDF »
Mechanistic Analysis of the Mitotic Kinesin Eg5.
J. C. Cochran, C. A. Sontag, Z. Maliga, T. M. Kapoor, J. J. Correia, and S. P. Gilbert (2004)
J. Biol. Chem. 279, 38861-38870
   Abstract »    Full Text »    PDF »
Distribution and functions of kinectin isoforms.
N. Santama, C. P. N. Er, L.-L. Ong, and H. Yu (2004)
J. Cell Sci. 117, 4537-4549
   Abstract »    Full Text »    PDF »
Polo-like Kinase-1 Is Required for Bipolar Spindle Formation but Is Dispensable for Anaphase Promoting Complex/Cdc20 Activation and Initiation of Cytokinesis.
M. A. T. M. van Vugt, B. C. M. van de Weerdt, G. Vader, H. Janssen, J. Calafat, R. Klompmaker, R. M. F. Wolthuis, and R. H. Medema (2004)
J. Biol. Chem. 279, 36841-36854
   Abstract »    Full Text »    PDF »
Eukaryotic Cells and their Cell Bodies: Cell Theory Revised.
F. BALUSKA, D. VOLKMANN, and P. W. BARLOW (2004)
Ann. Bot. 94, 9-32
   Abstract »    Full Text »    PDF »
Cytoplasmic Dynein Nucleates Microtubules to Organize Them into Radial Arrays In Vivo.
V. Malikov, A. Kashina, and V. Rodionov (2004)
Mol. Biol. Cell 15, 2742-2749
   Abstract »    Full Text »    PDF »
The arithmetic of centrosome biogenesis.
M. Delattre and P. Gonczy (2004)
J. Cell Sci. 117, 1619-1630
   Abstract »    Full Text »    PDF »
Microtubule Plus-End Dynamics in Xenopus Egg Extract Spindles.
J. S. Tirnauer, E. D. Salmon, and T. J. Mitchison (2004)
Mol. Biol. Cell 15, 1776-1784
   Abstract »    Full Text »    PDF »
Complete loss of the tumor suppressor MAD2 causes premature cyclin B degradation and mitotic failure in human somatic cells.
L. Michel, E. Diaz-Rodriguez, G. Narayan, E. Hernando, V. V. V. S. Murty, and R. Benezra (2004)
PNAS 101, 4459-4464
   Abstract »    Full Text »    PDF »
Expression of a Nondegradable Cyclin B1 Affects Plant Development and Leads to Endomitosis by Inhibiting the Formation of a Phragmoplast.
M. Weingartner, M.-C. Criqui, T. Meszaros, P. Binarova, A.-C. Schmit, A. Helfer, A. Derevier, M. Erhardt, L. Bogre, and P. Genschik (2004)
PLANT CELL 16, 643-657
   Abstract »    Full Text »    PDF »
Maternally expressed and partially redundant {beta}-tubulins in Caenorhabditis elegans are autoregulated.
G. C. Ellis, J. B. Phillips, S. O'Rourke, R. Lyczak, and B. Bowerman (2004)
J. Cell Sci. 117, 457-464
   Abstract »    Full Text »    PDF »
The Chromokinesin, KLP3A, Drives Mitotic Spindle Pole Separation during Prometaphase and Anaphase and Facilitates Chromatid Motility.
M. Kwon, S. Morales-Mulia, I. Brust-Mascher, G. C. Rogers, D. J. Sharp, and J. M. Scholey (2004)
Mol. Biol. Cell 15, 219-233
   Abstract »    Full Text »    PDF »
Aurora-A Kinase Maintains the Fidelity of Early and Late Mitotic Events in HeLa Cells.
T. Marumoto, S. Honda, T. Hara, M. Nitta, T. Hirota, E. Kohmura, and H. Saya (2003)
J. Biol. Chem. 278, 51786-51795
   Abstract »    Full Text »    PDF »
Hyperproliferation and p53 Status of Lens Epithelial Cells Derived from {alpha}B-crystallin Knockout Mice.
F. Bai, J. H. Xi, E. F. Wawrousek, T. P. Fleming, and U. P. Andley (2003)
J. Biol. Chem. 278, 36876-36886
   Abstract »    Full Text »    PDF »
NuSAP, a novel microtubule-associated protein involved in mitotic spindle organization.
T. Raemaekers, K. Ribbeck, J. Beaudouin, W. Annaert, M. Van Camp, I. Stockmans, N. Smets, R. Bouillon, J. Ellenberg, and G. Carmeliet (2003)
J. Cell Biol. 162, 1017-1029
   Abstract »    Full Text »    PDF »
The maternal-effect gene futile cycle is essential for pronuclear congression and mitotic spindle assembly in the zebrafish zygote.
M. P. S. Dekens, F. J. Pelegri, H.-M. Maischein, and C. Nusslein-Volhard (2003)
Development 130, 3907-3916
   Abstract »    Full Text »    PDF »
Dissecting the Cellular Functions of Annexin XI Using Recombinant Human Annexin XI-specific Autoantibodies Cloned by Phage Display.
L. Farnaes and H. J. Ditzel (2003)
J. Biol. Chem. 278, 33120-33126
   Abstract »    Full Text »    PDF »
Recovery, Visualization, and Analysis of Actin and Tubulin Polymer Flow in Live Cells: A Fluorescent Speckle Microscopy Study.
P. Vallotton, A. Ponti, C. M. Waterman-Storer, E. D. Salmon, and G. Danuser (2003)
Biophys. J. 85, 1289-1306
   Abstract »    Full Text »    PDF »
Molecular Phenotype of Spontaneously Arising 4N (G2-Tetraploid) Intermediates of Neoplastic Progression in Barrett's Esophagus.
M. T. Barrett, D. Pritchard, C. Palanca-Wessels, J. Anderson, B. J. Reid, and P. S. Rabinovitch (2003)
Cancer Res. 63, 4211-4217
   Abstract »    Full Text »    PDF »
A requirement for MAP kinase in the assembly and maintenance of the mitotic spindle.
M. M. Horne and T. M. Guadagno (2003)
J. Cell Biol. 161, 1021-1028
   Abstract »    Full Text »    PDF »
The condensin complex is required for proper spindle assembly and chromosome segregation in Xenopus egg extracts.
S. M. Wignall, R. Deehan, T. J. Maresca, and R. Heald (2003)
J. Cell Biol. 161, 1041-1051
   Abstract »    Full Text »    PDF »
Centrosomes Split in the Presence of Impaired DNA Integrity during Mitosis.
H. M.J. Hut, W. Lemstra, E. H. Blaauw, G. W.A. van Cappellen, H. H. Kampinga, and O. C.M. Sibon (2003)
Mol. Biol. Cell 14, 1993-2004
   Abstract »    Full Text »    PDF »
Spindle assembly and cytokinesis in the absence of chromosomes during Drosophila male meiosis.
E. Bucciarelli, M. G. Giansanti, S. Bonaccorsi, and M. Gatti (2003)
J. Cell Biol. 160, 993-999
   Abstract »    Full Text »    PDF »
Reduced survival of lens epithelial cells in the {alpha}A-crystallin-knockout mouse.
J. H. Xi, F. Bai, and U. P. Andley (2003)
J. Cell Sci. 116, 1073-1085
   Abstract »    Full Text »    PDF »
Minus-end capture of preformed kinetochore fibers contributes to spindle morphogenesis.
A. Khodjakov, L. Copenagle, M. B. Gordon, D. A. Compton, and T. M. Kapoor (2003)
J. Cell Biol. 160, 671-683
   Abstract »    Full Text »    PDF »
Microtubule Flux and Sliding in Mitotic Spindles of Drosophila Embryos.
I. Brust-Mascher and J. M. Scholey (2002)
Mol. Biol. Cell 13, 3967-3975
   Abstract »    Full Text »    PDF »
Reorganization of the microtubule array in prophase/prometaphase requires cytoplasmic dynein-dependent microtubule transport.
N. M. Rusan, U. S. Tulu, C. Fagerstrom, and P. Wadsworth (2002)
J. Cell Biol. 158, 997-1003
   Abstract »    Full Text »    PDF »
Computer simulations reveal motor properties generating stable antiparallel microtubule interactions.
F. Nedelec (2002)
J. Cell Biol. 158, 1005-1015
   Abstract »    Full Text »    PDF »
Human TPX2 is required for targeting Aurora-A kinase to the spindle.
T. A. Kufer, H. H.W. Sillje, R. Korner, O. J. Gruss, P. Meraldi, and E. A. Nigg (2002)
J. Cell Biol. 158, 617-623
   Abstract »    Full Text »    PDF »
The mitotic-spindle-associated protein astrin is essential for progression through mitosis.
J. Gruber, J. Harborth, J. Schnabel, K. Weber, and M. Hatzfeld (2002)
J. Cell Sci. 115, 4053-4059
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)