Self-organisation and forces in the microtubule cytoskeleton.

Modern microscopy techniques allow us to observe specifically tagged proteins in live cells. We can now see directly that many cellular structures, for example mitotic spindles, are in fact dynamic assemblies. Their apparent stability results from out-of-equilibrium stochastic interactions at the molecular level. Recent studies have shown that the spindles can form even after centrosomes are destroyed, and that they can even form around DNA-coated beads devoid of kinetochores. Moreover, conditions have been produced in which microtubule asters interact even in the absence of chromatin. Together, these observations suggest that the spindle can be experimentally deconstructed, and that its defining characteristics can be studied in a simplified context, in the absence of the full division machinery.

[1]  D. Smith,et al.  Active fluidization of polymer networks through molecular motors , 2002, Nature.

[2]  J. Tabony,et al.  Microtubule self-organization is gravity-dependent. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[3]  E. O'Toole,et al.  The spindle cycle in budding yeast , 2001, Nature Cell Biology.

[4]  D. Compton,et al.  Spindle assembly in animal cells. , 2000, Annual review of biochemistry.

[5]  M. Kirschner,et al.  Beyond self-assembly: From microtubules to morphogenesis , 1986, Cell.

[6]  François Nédélec,et al.  Dynamics of microtubule aster formation by motor complexes , 2001 .

[7]  G. C. Rogers,et al.  Functional coordination of three mitotic motors in Drosophila embryos. , 2000, Molecular biology of the cell.

[8]  J. Labbé,et al.  Germinal vesicle components are not required for the cell-cycle oscillator of the early starfish embryo. , 1988, Developmental biology.

[9]  M. Cross,et al.  Pattern formation outside of equilibrium , 1993 .

[10]  R. Wade,et al.  How does taxol stabilize microtubules? , 1995, Current Biology.

[11]  Sebastian A. Leidel,et al.  Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III , 2000, Nature.

[12]  Alexey Khodjakov,et al.  Centrosome-independent mitotic spindle formation in vertebrates , 2000, Current Biology.

[13]  M. McNiven,et al.  Organization of microtubules in centrosome-free cytoplasm , 1988, The Journal of cell biology.

[14]  E. Karsenti,et al.  Taxol-induced microtubule asters in mitotic extracts of Xenopus eggs: requirement for phosphorylated factors and cytoplasmic dynein , 1991, The Journal of cell biology.

[15]  Anthony A. Hyman,et al.  Structural changes at microtubule ends accompanying GTP hydrolysis: Information from a slowly hydrolyzable analogue of GTP, guanylyl (α,β)methylenediphosphonate , 1998 .

[16]  A. Hyman,et al.  Role of GTP hydrolysis in microtubule dynamics: information from a slowly hydrolyzable analogue, GMPCPP. , 1992, Molecular biology of the cell.

[17]  Yixian Zheng,et al.  Ran stimulates spindle assembly by altering microtubule dynamics and the balance of motor activities , 2001, Nature Cell Biology.

[18]  G. C. Rogers,et al.  Microtubule motors in mitosis , 2000, Nature.

[19]  S. Ikegami,et al.  Achromosomal cleavage of fertilized starfish eggs in the presence of aphidicolin. , 1981, Developmental biology.

[20]  Torsten Wittmann,et al.  The spindle: a dynamic assembly of microtubules and motors , 2001, Nature Cell Biology.

[21]  Iain W. Mattaj,et al.  Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation , 1999, Nature.

[22]  E. Karsenti Mitotic spindle morphogenesis in animal cells. , 1991, Seminars in cell biology.

[23]  A. Zhabotinsky,et al.  Concentration Wave Propagation in Two-dimensional Liquid-phase Self-oscillating System , 1970, Nature.

[24]  François Nédélec,et al.  Computer simulations reveal motor properties generating stable antiparallel microtubule interactions , 2002, The Journal of cell biology.

[25]  J. Kubiak,et al.  Bipolar meiotic spindle formation without chromatin , 1998, Current Biology.

[26]  Anthony A. Hyman,et al.  Polarity controls forces governing asymmetric spindle positioning in the Caenorhabditis elegans embryo , 2001, Nature.

[27]  George N. Reeke,et al.  BOOK REVIEW: "SELF-ORGANIZATION IN BIOLOGICAL SYSTEMS" BY S. CAMAZINE, J. DENEUBOURG, N. R. FRANKS, J. SNEYD, G. THERAULAZ AND E. BONABEAU , 2002 .

[28]  E. Smirnova,et al.  Spindle poles in higher plant mitosis. , 1992, Cell motility and the cytoskeleton.

[29]  Yixian Zheng,et al.  Stimulation of microtubule aster formation and spindle assembly by the small GTPase Ran. , 1999, Science.

[30]  E. Salmon,et al.  Checkpoint signals in grasshopper meiosis are sensitive to microtubule attachment, but tension is still essential. , 2001, Journal of cell science.

[31]  Marie-France Carlier,et al.  Mechanism of Actin-Based Motility , 2001, Science.

[32]  A. Lambert Microtubule-organizing centers in higher plants. , 1993, Current opinion in cell biology.

[33]  I. Prigogine,et al.  Formative Processes. (Book Reviews: Self-Organization in Nonequilibrium Systems. From Dissipative Structures to Order through Fluctuations) , 1977 .

[34]  Iain W. Mattaj,et al.  Ran–GTP coordinates regulation of microtubule nucleation and dynamics during mitotic-spindle assembly , 2001, Nature Cell Biology.

[35]  Eric Karsenti,et al.  Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts , 1996, Nature.

[36]  I. Hagan,et al.  Forces acting on the fission yeast anaphase spindle. , 1996, Cell motility and the cytoskeleton.

[37]  S. Leibler,et al.  Assembly and positioning of microtubule asters in microfabricated chambers. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[38]  Karsten Weis,et al.  Visualization of a Ran-GTP Gradient in Interphase and Mitotic Xenopus Egg Extracts , 2002, Science.

[39]  B. Yurke,et al.  Measurement of the force-velocity relation for growing microtubules. , 1997, Science.

[40]  T. Mitchison,et al.  Self-organization of polymer-motor systems in the cytoskeleton. , 1992, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[41]  J. Schnakenberg,et al.  G. Nicolis und I. Prigogine: Self‐Organization in Nonequilibrium Systems. From Dissipative Structures to Order through Fluctuations. J. Wiley & Sons, New York, London, Sydney, Toronto 1977. 491 Seiten, Preis: £ 20.–, $ 34.– , 1978 .

[42]  A. Hyman,et al.  Morphogenetic Properties of Microtubules and Mitotic Spindle Assembly , 1996, Cell.

[43]  A. Hyman,et al.  Structural Changes Accompanying Gtp Hydrolysis in Microtubules: Information from a Slowly Hydrolyzable Analogue Guanylyl-(c ,/3)-methylene-diphosphonate , 1995 .

[44]  M. Bornens,et al.  Centrosome reproduction in vitro: mammalian centrosomes in Xenopus lysates. , 2001, Methods in cell biology.

[45]  V. Malikov,et al.  Self-organization of a radial microtubule array by dynein-dependent nucleation of microtubules , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[46]  M. Kirschner,et al.  Role of the centrosome in organizing the interphase microtubule array: properties of cytoplasts containing or lacking centrosomes , 1984, The Journal of cell biology.

[47]  T. Mitchison,et al.  Microtubule polymerization dynamics. , 1997, Annual review of cell and developmental biology.

[48]  C. Rieder,et al.  Separating centrosomes interact in the absence of associated chromosomes during mitosis in cultured vertebrate cells. , 2002, Cell motility and the cytoskeleton.

[49]  S. Haggarty,et al.  Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. , 1999, Science.

[50]  S. Fuller,et al.  Structure of growing microtubule ends: two-dimensional sheets close into tubes at variable rates , 1995, The Journal of cell biology.

[51]  G. Borisy,et al.  Self-centring activity of cytoplasm , 1997, Nature.

[52]  S. Leibler,et al.  Physical Properties Determining Self-Organization of Motors and Microtubules , 2001, Science.

[53]  I. Vernos,et al.  A model for the proposed roles of different microtubule-based motor proteins in establishing spindle bipolarity , 1998, Current Biology.

[54]  R. Nicklas,et al.  The impact of chromosomes and centrosomes on spindle assembly as observed in living cells , 1995, The Journal of cell biology.

[55]  G. Borisy,et al.  Microtubule Treadmilling in Vivo , 1997, Science.

[56]  R. Vale,et al.  The way things move: looking under the hood of molecular motor proteins. , 2000, Science.

[57]  T. Mitchison,et al.  Anaphase A Chromosome Movement and Poleward Spindle Microtubule Flux Occur At Similar Rates in Xenopus Extract Spindles , 1998, The Journal of cell biology.

[58]  T. Mitchison,et al.  Polewards microtubule flux in the mitotic spindle: evidence from photoactivation of fluorescence , 1989, The Journal of cell biology.

[59]  E. Smirnova,et al.  Microtubule converging centers and reorganization of the interphase cytoskeleton and the mitotic spindle in higher plant Haemanthus. , 1994, Cell motility and the cytoskeleton.