Résumés
Résumé
Les microtubules sont, à chaque division cellulaire, organisés en fuseau bipolaire pour assurer la transmission des chromosomes aux cellules filles. Dès la sortie d’interphase, les microtubules deviennent extrêmement labiles, ce qui facilite leur réorganisation. Parallèlement, des mécanismes de restabilisation locale des microtubules doivent être mis en place pour l’assemblage du fuseau. Tout d’abord, la chromatine favorise la polymérisation et la stabilisation des microtubules autour d’elle. Cet « effet chromatine » est principalement relayé par une enzyme, la GTPase Ran. Il est renforcé par l’activité de moteurs moléculaires liés à la chromatine, qui ancrent des microtubules aux bras des chromosomes. Enfin, les kinétochores, structures protéiques accolées à une région limitée de la chromatine, stabilisent d’autres microtubules qui s’organisent en « fibres kinétochoriennes » robustes et contribuent au maintien du fuseau bipolaire dans la cellule.
Summary
The partition of the genetic material of cells in two identical lots during cell division relies on the assembly of a structure composed of microtubules, the bipolar spindle. As a cell prepares its division, changes in the state of its cytoplasm lead to the disassembly and to the global instability of its microtubule network. However, in order for the spindle to form, its microtubules must persist amid this destabilizing cytoplasm. A large body of experimental data now shows that the chromosomes themselves are the source of this persistence. They carry out this task through a chromatin-induced reversal of the dominating microtubule depolymerization regime, thereby resulting in a net microtubule polymerization locally around chromosomes, and through the capture, by kinetochores, of microtubules associated to each spindle pole and the assembly of kinetochore-associated microtubule bundles (K-fibres). In this review, we discuss the mechanisms and molecules that allow chromosomes to locally induce microtubule polymerization and stabilization during spindle assembly.
Parties annexes
Références
- 1. Earnshaw WC, Bernat RL. Chromosomal passengers: toward an integrated view of mitosis.Chromosoma 1991; 100: 139-46.
- 2. Wittmann T, Hyman A, Desai A. The spindle: a dynamic assembly of microtubules and motors. Nat Cell Biol 2001. 3: E28-34.
- 3. Desai A, Mitchison TJ. Microtubule polymerization dynamics. Annu Rev Cell Dev Biol 1997; 13: 83-117.
- 4. Le Peuch C, Dorée M. Le temps du cycle cellulaire.Med Sci 2000; 16: 461-8.
- 5. Verde F, Labbé JC, Dorée M, Karsenti E. Regulation of microtubule dynamics by cdc2 protein kinase in cell-free extracts of Xenopus eggs.Nature 1990; 343: 233-8.
- 6. Vasquez RJ, Gard DL, Cassimeris L. Phosphorylation by CDK1 regulates XMAP215 function in vitro.Cell Motil Cytoskeleton 1999; 43: 310-21.
- 7. Karsenti E. Vers une description du mécanisme d’assemblage du fuseau mitotique à l’échelle moléculaire. Med Sci 1993; 9: 131-9.
- 8. Nicklas RB, Gordon GW. The total length of spindle microtubules depends on the number of chromosomes present.J Cell Biol 1985; 100: 1-7.
- 9. Zhang D, Nicklas RB. Chromosomes initiate spindle assembly upon experimental dissolution of the nuclear envelope in grasshopper spermatocytes. J Cell Biol 1995; 131: 1125-31.
- 10. Sawin KE, Mitchison TJ. Mitotic spindle assembly by two different pathways in vitro.J Cell Biol 1991; 112: 925-40.
- 11. Dogterom M, Felix MA, Guet CC, Leibler S. Influence of M-phase chromatin on the anisotropy of microtubule asters. J Cell Biol 1996; 133: 125-40.
- 12. Karsenti E, Newport J, Kirschner M. Respective roles of centrosomes and chromatin in the conversion of microtubule arrays from interphase to metaphase.J Cell Biol 1984; 99: 47s-54.
- 13. Heald R, Tournebize R, Blank T, et al. Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts.Nature 1996; 382: 420-5.
- 14. Karsenti E. Mitotic spindle morphogenesis in animal cells.Semin Cell Biol 1991; 2: 251-60.
- 15. Khodjakov A, Cole RW, Oakley BR, Rieder CL. Centrosome-independent mitotic spindle formation in vertebrates. Curr Biol 2000; 10: 59-67.
- 16. Lawler S. Microtubule dynamics: if you need a shrink try stathmin/Op18.Curr Biol 1998; 8: R212-4.
- 17. Andersen SS, Ashford AJ, Tournebize R, et al. Mitotic chromatin regulates phosphorylation of Stathmin/Op18.Nature 1997; 389: 640-3.
- 18. Budde PP, Kumagi A, Dunphy WG, Heald R. Regulation of Op18 during spindle assembly in Xenopus egg extracts. J Cell Biol 2001; 153: 149-58.
- 19. Carazo-Salas RE. Ran ou le parfum de la chromatine.Med Sci 2001; 17: 1056-60.
- 20. Mattaj IW, Englmeier L. Nucleocytoplasmic transport: the soluble phase.Annu Rev Biochem 1998; 67: 265-306.
- 21. Dorseuil O. Petite protéine G Ran et contrôle de l’import-export nucléaire.Med Sci 1998; 14: 85-9.
- 22. Carazo-Salas RE, et al. Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation.Nature 1999. 400: 178-81.
- 23. Carazo-Salas RE, Guarguaglini G, Gruss OJ, et al. Ran-GTP coordinates regulation of microtubule nucleation and dynamics during mitotic-spindle assembly. Nat Cell Biol 2001; 3: 228-34.
- 24. Guarguaglini G, Renzi L, D’Ottavio F, et al. Regulated Ran-binding protein 1 activity is required for organization and function of the mitotic spindle in mammalian cells in vivo.Cell Growth Differ 2000; 11: 455-65.
- 25. Fleig, U, Salus SS, Karig I, Sazer S. The fission yeast ran GTPase is required for microtubule integrity.J Cell Biol 2000; 151: 1101-11.
- 26. Endow SA. Microtubule motors in spindle and chromosome motility.Eur J Biochem 1999; 262: 12-8.
- 27. Antonio C, Ferby I, Wilhelm H, et al. Xkid, a chromokinesin required for chromosome alignment on the metaphase plate.Cell 2000; 102: 425-35.
- 28. Vernos I, Raats J, Hirano T, et al. Xklp1, a chromosomal Xenopus kinesin-like protein essential for spindle organization and chromosome positioning.Cell 1995; 81: 117-27.
- 29. Theurkauf WE, Hawley RS. Meiotic spindle assembly in Drosophila females: behavior of nonexchange chromosomes and the effects of mutations in the nod kinesin-like protein.J Cell Biol 1992; 116: 1167-80.
- 30. Bloom K. The centromere frontier: kinetochore components, microtubule-based motility, and the CEN-value paradox. Cell 1993; 73: 621-4.
- 31. Nicklas RB, Kubai DF, Hays TS. Spindle microtubules and their mechanical associations after micromanipulation in anaphase.J Cell Biol 1982; 95: 91-104.
- 32. Yao X., Abrieu A, Zheng Y, et al. CENP-E forms a link between attachment of spindle microtubules to kinetochores and the mitotic checkpoint. Nat Cell Biol 2000; 2: 484-91.
- 33. McEwen BF, Chan GK, Zubrowski B, et al. CENP-E is essential for reliable bioriented spindle attachment, but chromosome alignment can be achieved via redundant mechanisms in mammalian cells. Mol Biol Cell 2001; 12: 2776-89.
- 34. Cassimeris L, Salmon ED. Kinetochore microtubules shorten by loss of subunits at the kinetochores of prometaphase chromosomes.J Cell Sci 1991; 98: 151-8.
- 35. Khodjakov A., Gabashvili IS, Rieder CL. « Dumb » versus « smart » kinetochore models for chromosome congression during mitosis in vertebrate somatic cells.Cell Motil Cytoskeleton 1999; 43: 179-85.
- 36. Desai A, Maddox PS, Mitchison TJ, et al. Anaphase A chromosome movement and poleward spindle microtubule flux occur At similar rates in Xenopus extract spindles. J Cell Biol 1998; 141: 703-13.
- 37. Kirschner M, Mitchison T. Beyond self-assembly: from microtubules to morphogenesis.Cell 1986; 45: 329-42.
- 38. Dujardin D, Wacker UI, Moreau A, et al. Evidence for a role of CLIP-170 in the establishment of metaphase chromosome alignment.J Cell Biol 1998; 141: 849-62.
- 39. Rieder CL, Alexander SP. Kinetochores are transported poleward along a single astral microtubule during chromosome attachment to the spindle in newt lung cells.J Cell Biol 1990; 110: 81-95.
- 40. Wojcik E, Basto R, Serr M, et al. Kinetochore dynein: its dynamics and role in the transport of the Rough deal checkpoint protein.Nat Cell Biol 2001; 3: 1001-7.
- 41. Schaar BT, Chan GK, Maddox R, et al. CENP-E function at kinetochores is essential for chromosome alignment.J Cell Biol 1997; 139: 1373-82.
- 42. Lombillo VA, Stewart RJ, Mc Intosh JR, et al. Antibodies to the kinesin motor domain and CENP-E inhibit microtubule depolymerization-dependent motion of chromosomes in vitro.J Cell Biol 1995; 128: 107-15.
- 43. Wordeman L, Mitchison TJ. Identification and partial characterization of mitotic centromere- associated kinesin, a kinesin-related protein that associates with centromeres during mitosis. J Cell Biol 1995; 128: 95-104.
- 44. Walczak CE, Mitchison TJ, Desai A. XKCM1: a Xenopus kinesin-related protein that regulates microtubule dynamics during mitotic spindle assembly. Cell 1996; 84: 37-47.
- 45. Maney T, Hunter AW, Wagenbach M, Wordeman L. Mitotic centromere-associated kinesin is important for anaphase chromosome segregation. J Cell Biol 1998; 142: 787-801.
- 46. Kalab P, Weis K, Heald R.Vizualisation of a Ran-GTP gradient in interphase and mitotic Xenopus egg extracts. Science 2002; 295: 2452-6.