Cell News 3/2013
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bound and that their components are in constant exchange with
the surrounding cytoplasm. These biophysical studies are con-
sistent with the emerging concept that phase separation is an
important physical principle for organizing the internal structu-
res of cells
40
. In the context of our studies, we can thus think of
a spindle as an active liquid crystal drop that is phase separated
from the cytoplasm. In this case, the formation of the second
phase is initiated by chromatin, which induces local nucleation
of microtubules. While the microtubule phase is forming, other
components can segregate into this phase where they can mo-
dulate spindle assembly, dynamics, and shape.
Acknowledgments
I thank all the present and past members of the Hyman lab, and
my colleagues at the MPI-CBG and MPI-PKS. My work was sup-
ported by the European Commission's 7th Framework Program-
me grant Systems Biology of Stem Cells and Reprogramming
(HEALTH-F7-2010-242129/SyBoSS).
References
1.
Nigg, E. A. & Stearns, T. The centrosome cycle: Centriole biogenesis, duplication and
inherent asymmetries. Nature Cell Biology 13, 1154–1160 (2011).
2.
Bettencourt-Dias, M., Hildebrandt, F., Pellman, D., Woods, G. & Godinho, S. A. Centroso-
mes and cilia in human disease. Trends Genet. 27, 307–315 (2011).
3.
Moyes, C. D. Controlling muscle mitochondrial content. J. Exp. Biol. 206, 4385–4391
(2003).
4.
Wiest, D. L. et al. Membrane biogenesis during B cell differentiation: most endoplasmic
reticulum proteins are expressed coordinately. J Cell Biol 110, 1501–1511 (1990).
5.
Marshall, W. F. Origins of cellular geometry. BMC Biol 9, 57 (2011).
6.
Libbrecht, K. G. The physics of snow crystals. Rep. Prog. Phys. 68, 855–895 (2005).
7.
Berdahl, A., Torney, C. J., Ioannou, C. C., Faria, J. J. & Couzin, I. D. Emergent sensing of
complex environments by mobile animal groups. Science 339, 574–576 (2013).
8.
Montorzi, M., Burgos, M. H. & Falchuk, K. H.
Xenopus
laevis embryo development: arrest
of epidermal cell differentiation by the chelating agent 1,10-phenanthroline. Mol Reprod
Dev 55, 75–82 (2000).
9.
Dumont, J. et al. A centriole- and RanGTP-independent spindle assembly pathway in
meiosis I of vertebrate oocytes. J Cell Biol 176, 295–305 (2007).
10. Helmke, K. J., Heald, R. & Wilbur, J. D. Interplay between spindle architecture and func-
tion. Int Rev Cell Mol Biol 306, 83–125 (2013).
11. Isenberg, I. On the theory of the nematic phase and its possible relation to the mitotic
spindle structure. Bulletin of Mathematical Biophysics 16, 83–96 (1954).
12. Gatlin, J. C. et al. Spindle fusion requires dynein-mediated sliding of oppositely oriented
microtubules. Curr Biol 19, 287–296 (2009).
13. Dumont, S. & Mitchison, T. J. Compression regulates mitotic spindle length by a mecha-
nochemical switch at the poles. Curr Biol 19, 1086–1095 (2009).
14. Gatlin, J. C. & Bloom, K. Microtubule motors in eukaryotic spindle assembly and mainte-
nance. Semin. Cell Dev. Biol. 21, 248–254 (2010).
15. Itabashi, T. et al. Probing the mechanical architecture of the vertebrate meiotic spindle.
Nat Meth 6, 167–172 (2009).
16. Shimamoto, Y., Maeda, Y. T., Ishiwata, S., Libchaber, A. J. & Kapoor, T. M. Insights into the
micromechanical properties of the metaphase spindle. Cell 145, 1062–1074 (2011).
17. Reber, S. B. et al. XMAP215 activity sets spindle length by controlling the total mass of
spindle microtubules. Nature Cell Biology 9, 1116-22 (2013).
18. Brouhard, G. J. et al. XMAP215 is a processive microtubule polymerase. Cell 132, 79–88
(2008).
19. Gard, D. L. & Kirschner, M. W. A microtubule-associated protein from
Xenopus
eggs that
specifically promotes assembly at the plus-end. J Cell Biol 105, 2203–2215 (1987).
20. Wang, P. J. & Huffaker, T. C. Stu2p: A microtubule-binding protein that is an essential
component of the yeast spindle pole body. J Cell Biol 139, 1271–1280 (1997).
21. Nakaseko, Y., Goshima, G., Morishita, J. & Yanagida, M. M phase-specific kinetochore
proteins in fission yeast: microtubule-associating Dis1 and Mtc1 display rapid separation
and segregation during anaphase. Curr Biol 11, 537–549 (2001).
22. Garcia, M. A., Vardy, L., Koonrugsa, N. & Toda, T. Fission yeast ch-TOG/XMAP215 ho-
mologue Alp14 connects mitotic spindles with the kinetochore and is a component of the
Mad2-dependent spindle checkpoint. EMBO J 20, 3389–3401 (2001).
23. Whittington, A. T. et al. MOR1 is essential for organizing cortical microtubules in plants.
Nature 411, 610–613 (2001).
24. Matthews, L. R., Carter, P., Thierry-Mieg, D. & Kemphues, K. ZYG-9, a Caenorhabditis ele-
gans protein required for microtubule organization and function, is a component of meiotic
and mitotic spindle poles. J Cell Biol 141, 1159–1168 (1998).
25. Cullen, C. F., Deak, P., Glover, D. M. & Ohkura, H. mini spindles: A gene encoding a con-
served microtubule-associated protein required for the integrity of the mitotic spindle in
Drosophila. J Cell Biol 146, 1005–1018 (1999).
26. Charrasse, S. et al. The TOGp protein is a new human microtubule-associated protein
homologous to the
Xenopus
XMAP215. J Cell Sci 111 ( Pt 10), 1371–1383 (1998).
27. Al-Bassam, J., Larsen, N. A., Hyman, A. A. & Harrison, S. C. Crystal structure of a TOG do-
main: conserved features of XMAP215/Dis1-family TOG domains and implications for tubulin
binding. Structure 15, 355–362 (2007).
28. Ovechkina, Y., Wagenbach, M. & Wordeman, L. K-loop insertion restores microtubule
depolymerizing activity of a ‘neckless’ MCAK mutant. J Cell Biol 159, 557–562 (2002).
29. Widlund, P. O. et al. XMAP215 polymerase activity is built by combining multiple tu-
bulin-binding TOG domains and a basic lattice-binding region. Proceedings of the National
Academy of Sciences 108, 2741–2746 (2011).
30. Wuehr, M. et al. Evidence for an upper limit to mitotic spindle length. Current Biology
18, 1256–1261 (2008).
31. Budde, P. P., Kumagai, A., Dunphy, W. G. & Heald, R. Regulation of Op18 during spindle
assembly in
Xenopus
egg extracts. J Cell Biol 153, 149–158 (2001).
32. Gaetz, J. Dynein/dynactin regulate metaphase spindle length by targeting depolymeri-
zing activities to spindle poles. J Cell Biol 166, 465–471 (2004).
33. Goshima, G. et al. Genes required for mitotic spindle assembly in Drosophila S2 cells.
Science 316, 417–421 (2007).
34. Bird, A. W. & Hyman, A. A. Building a spindle of the correct length in human cells requi-
res the interaction between TPX2 and Aurora A. J Cell Biol 182, 289–300 (2008).
35. Brust-Mascher, I., Sommi, P., Cheerambathur, D. K. & Scholey, J. M. Kinesin-5-dependent
Poleward Flux and Spindle Length Control in Drosophila Embryo Mitosis. Mol Biol Cell 20,
1749–1762 (2009).
36. Loughlin, R., Wilbur, J. D., McNally, F. J., Nédélec, F. J. & Heald, R. Katanin contributes to
interspecies spindle length scaling in
Xenopus
. Cell 147, 1397–1407 (2011).
37. Brangwynne, C. P. et al. Germline P granules are liquid droplets that localize by cont-
rolled dissolution/condensation. Science 324, 1729–1732 (2009).
38. Brangwynne, C. P., Mitchison, T. J. & Hyman, A. A. Active liquid-like behavior of nucleoli
determines their size and shape in
Xenopus
laevis oocytes. Proc Natl Acad Sci USA 108,
4334–4339 (2011).
39. Decker, M. et al. Limiting amounts of centrosome material set centrosome size in C.
elegans embryos. Curr Biol 21, 1259–1267 (2011).
40. Li, P. et al. Phase transitions in the assembly of multivalent signalling proteins. Nature
483, 336–340 (2012).
Simone Reber studied Biology
at the University of Heidel-
berg, from where she also re-
ceived her PhD. Since then
she has been interested in
understanding the biochemi-
cal and biophysical principles
that underlie the self-organi-
zation of the mitotic spindle
mainly using
Xenopus laevis
as a model system. In 2008,
she joined the lab of Tony Hy-
man at the Max-Planck-Institute for Molecular Cell Biology and
Genetics in Dresden. Together with the lab of Frank Jülicher at
the Max-Planck-Institute for the Physics of Complex Systems,
she started combing theory and experiment to achieve a systems
understanding of spindle assembly, organization, and function.
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