Skip to main content
SpringerLink
Log in

Factors that Control Mitotic Spindle Dynamics

  • Chapter
  • First Online:
Protein Reviews

Part of the book series: Advances in Experimental Medicine and Biology ((PROTRE,volume 925))

Abstract

Mitosis is the last phase of the cell cycle and it leads to the formation of two daughter cells with the same genetic information. This process must occurr in a very precise way and this task is essential to preserve genetic stability and to maintain cell viability. Accurate chromosome segregation during mitosis is brought about by an important cellular organelle: the mitotic spindle. This structure is made of microtubules, polymers of alpha and beta tubulin, and it is highly dynamic during the cell cycle: it emanates from two microtubules organizing centers (Spindle Pole Bodies, SPBs, in yeast) that are essential to build a short bipolar spindle, and it undergoes two steps of elongation during anaphase A and anaphase B in order to separate sister chromatids. Several proteins are involved in the control of mitotic spindle dynamics and their activity is tightly coordinated with other cell cycle events and with cell cycle progression.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

APC:

Anaphase Promoting Complex

CDK:

cyclin dependent kinase

cMTs:

cytoplasmic microtubules

CPCs:

chromosome passenger complexes

EM:

electron microscopy

FEAR:

Cdc-Fourteen Early Anaphase Release pathway

kMTs:

kinetochore MTs

MAP:

microtubule-associated protein

MEN:

Mitotic Exit Network

MTs:

microtubules

nMTs:

nuclear MTs

SAC:

spindle assembly checkpoint

SPB:

Spindle Pole Bodies

References

  • Adams IR, Kilmartin JV (1999) Localization of core spindle pole body (SPB) components during SPB duplication in Saccharomyces cerevisiae. J Cell Biol 145(4):809–823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adams RR, Carmena M, Earnshaw WC (2001) Chromosomal passengers and the (aurora) ABCs of mitosis. Trends Cell Biol 11(2):49–54

    Article  CAS  PubMed  Google Scholar 

  • Booher RN, Deshaies RJ, Kirschner MW (1993) Properties of Saccharomyces cerevisiae wee1 and its differential regulation of p34CDC28 in response to G1 and G2 cyclins. EMBO J 12(9):3417–3426

    CAS  PubMed  PubMed Central  Google Scholar 

  • Breitkreutz A, Choi H, Sharom JR, Boucher L, Neduva V, Larsen B, Lin ZY, Breitkreutz BJ, Stark C, Liu G, Ahn J, Dewar-Darch D, Reguly T, Tang X, Almeida R, Qin ZS, Pawson T, Gingras AC, Nesvizhskii AI, Tyers M (2010) A global protein kinase and phosphatase interaction network in yeast. Science 328(5981):1043–1046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bullitt E, Rout M, Kilmartin J, Akey C (1997) The yeast spindle pole body is assembled around a central crystal of Spc42p. Cell 89:1077–1086

    Article  CAS  PubMed  Google Scholar 

  • Carvalho P, Tirnauer JS, Pellman D (2003) Surfing on microtubule ends. Trends Cell Biol 13:229–237

    Article  CAS  PubMed  Google Scholar 

  • Carvalho P, Gupta ML Jr, Hoyt MA, Pellman D (2004) Cell cycle control of kinesin-mediated transport of Bik1 (CLIP-170) regulates microtubule stability and dynein activation. Dev Cell 6:815–829

    Article  CAS  PubMed  Google Scholar 

  • Chiroli E, Rancati G, Catusi I, Lucchini G, Piatti S (2009) Cdc14 inhibition by the spindle assembly checkpoint prevents unscheduled centrosome separation in budding yeast. Mol Biol Cell 20(10):2626–2637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clarke DJ, Bachant J (2008) Kinetochore structure and spindle assembly checkpoint signaling in the budding yeast, Saccharomyces cerevisiae. Front Biosci 13:6787–6819

    Article  CAS  PubMed  Google Scholar 

  • Crasta K, Huang P, Morgan G, Winey M, Surana U (2006) Cdk1 regulates centrosome separation by restraining proteolysis of microtubule-associated proteins. EMBO J 25(11):2551–2563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crasta K, Lim HH, Giddings TH Jr, Winey M, Surana U (2008) Inactivation of Cdh1 by synergistic action of Cdk1 and polo kinase is necessary for proper assembly of the mitotic spindle. Nat Cell Biol 10(6):665–675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Simone A, Nédélec F, Gönczy P (2016) Dynein transmits polarized actomyosin cortical flows to promote centrosome separation. Cell Rep 14(9):2250–2262

    Article  PubMed  Google Scholar 

  • Gheber L, Kuo SC, Hoyt MA (1999) Motile properties of the kinesin-related Cin8p spindle motor extracted from Saccharomyces cerevisiae cells. J Biol Chem 274:9564–9572

    Article  CAS  PubMed  Google Scholar 

  • Gupta ML Jr, Carvalho P, Roof DM, Pellman D (2006) Plus end-specific depolymerase activity of Kip3, a kinesin-8 protein, explains its role in positioning the yeast mitotic spindle. Nat Cell Biol 8:913–923

    Article  CAS  PubMed  Google Scholar 

  • Haase SB, Winey M, Reed SI (2001) Multi-step control of spindle pole body duplication by cyclin-dependent-kinase. Nat Cell Biol 3:38–42

    Article  CAS  PubMed  Google Scholar 

  • Higuchi T, Uhlmann F (2005) Stabilization of microtubule dynamics at anaphase onset promotes chromosome segregation. Nature 433(7022):171–176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hildebrandt ER, Hoyt MA (2000) Mitotic motors in Saccharomyces cerevisiae. Biochim Biophys Acta 1496:99–116

    Article  CAS  PubMed  Google Scholar 

  • Hildebrandt ER, Hoyt MA (2001) Cell cycle-dependent degradation of the Saccharomyces cerevisiae spindle motor Cin8p requires APC(Cdh1) and a bipartite destruction sequence. Mol Biol Cell 12(11):3402–3416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hwang E, Kusch J, Barral Y, Huffaker TC (2003) Spindle orientation in Saccharomyces cerevisiae depends on the transport of microtubule ends along polarized actin cables. J Cell Biol 161:483–488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jacobs CW, Adams AE, Szaniszlo PJ, Pringle JR (1988) Functions of microtubules in the Saccharomyces cerevisiae cell cycle. J Cell Biol 107:1409–1426

    Article  CAS  PubMed  Google Scholar 

  • Jaspersen SL, Winey M (2004) The budding yeast spindle pole body: structure, duplication, and function. Annu Rev Cell Dev Biol 20:1–28

    Article  CAS  PubMed  Google Scholar 

  • Juanes MA, ten Hoopen R, Segal M (2011) Ase1p phosphorylation by cyclin-dependent kinase promotes correct spindle assembly in S. cerevisiae. Cell Cycle 10(12):1988–1997

    Article  CAS  PubMed  Google Scholar 

  • Juang YL, Huang J, Peters JM, McLaughlin ME, Tai CY, Pellman D (1997) APC-mediated proteolysis of Ase1 and the morphogenesis of the mitotic spindle. Science 275:1311–1314

    Article  CAS  PubMed  Google Scholar 

  • Kahana JA, Schlenstedt G, Evanchuk DM, Geiser JR, Hoyt MA, Silver PA (1998) The yeast dynactin complex is involved in partitioning the mitotic spindle between mother and daughter cells during anaphase B. Mol Biol Cell 9(7):1741–1756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kellogg DR (2003) Wee1-dependent mechanisms required for coordination of cell growth and cell division. J Cell Sci 116(Pt 24):4883–4890

    Article  CAS  PubMed  Google Scholar 

  • Khmelinskii A, Schiebel E (2008) Assembling the spindle midzone in the right place at the right time. Cell Cycle 7:283–286

    Article  CAS  PubMed  Google Scholar 

  • Khmelinskii A, Lawrence C, Roostalu J, Schiebel E (2007) Cdc14-regulated midzone assembly controls anaphase B. J Cell Biol 177:981–993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khmelinskii A, Roostalu J, Roque H, Antony C, Schiebel E (2009) Phosphorylation-dependent protein interactions at the spindle midzone mediate cell cycle regulation of spindle elongation. Dev Cell 17:244–256

    Article  CAS  PubMed  Google Scholar 

  • Khodjakov A, La Terra S, Chang F (2004) Laser microsurgery in fission yeast; role of the mitotic spindle midzone in anaphase B. Curr Biol 14(15):1330–1340

    Article  CAS  PubMed  Google Scholar 

  • King K, Kang H, Jin M, Lew DJ (2013) Feedback control of Swe1p degradation in the yeast morphogenesis checkpoint. Mol Biol Cell 24(7):914–922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kosco KA, Pearson CG, Maddox PS, Wang PJ, Adams IR, Salmon ED, Bloom K, Huffaker TC (2001) Control of microtubule dynamics by Stu2p is essential for spindle orientation and metaphase chromosome alignment in yeast. Mol Biol Cell 12(9):2870–2880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kotwaliwale CV, Frei SB, Stern BM, Biggins S (2007) A pathway containing the Ipl1/aurora protein kinase and the spindle midzone protein Ase1 regulates yeast spindle assembly. Dev Cell 13(3):433–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee WL, Kaiser MA, Cooper JA (2005) The offloading model for dynein function: differential function of motor subunits. J Cell Biol 168:201–207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maddox P, Straight A, Coughlin P, Mitchison TJ, Salmon ED (2003) Direct observation of microtubule dynamics at kinetochores in Xenopus extract spindles implications for spindle mechanics. J Cell Biol 162(3):377–382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maiato H, Khodjakov A, Rieder CL (2005) Drosophila CLASP is required for the incorporation of microtubule subunits into fluxing kinetochore fibres. Nat Cell Biol 7:42–47

    Article  CAS  PubMed  Google Scholar 

  • Martinez JS, Jeong DE, Choi E, Billings BM, Hall MC (2006) Acm1 is a negative regulator of the CDH1-dependent anaphase-promoting complex/cyclosome in budding yeast. Mol Cell Biol 26(24):9162–9176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McMillan JN, Theesfeld CL, Harrison JC, Bardes ES, Lew DJ (2002) Determinants of Swe1p degradation in Saccharomyces cerevisiae. Mol Biol Cell 13(10):3560–3575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mendoza M, Norden C, Durrer K, Rauter H, Uhlmann F, Barral Y (2009) A mechanism for chromosome segregation sensing by the NoCut checkpoint. Nat Cell Biol 11:477–483

    Article  CAS  PubMed  Google Scholar 

  • Molk JN, Bloom K (2006) Microtubule dynamics in the budding yeast mating pathway. J Cell Sci 119:3485–3490

    Article  CAS  PubMed  Google Scholar 

  • Moore JK, Stuchell-Brereton MD, Cooper JA (2009) Function of dynein in budding yeast: mitotic spindle positioning in a polarized cell. Cell Motil Cytoskeleton 66:546–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Norden C, Mendoza M, Dobbelaere J, Kotwaliwale CV, Biggins S, Barral Y (2006) The NoCut pathway links completion of cytokinesis to spindle midzone function to prevent chromosome breakage. Cell 125(1):85–98

    Article  CAS  PubMed  Google Scholar 

  • O’Toole E, Winey M, McIntosh JR (1999) High-voltage electron tomography of spindle pole bodies and early mitotic spindles in the yeast Saccharomyces cerevisiae. Mol Biol Cell 10:2017–2031

    Article  PubMed  PubMed Central  Google Scholar 

  • Pasqualone D, Huffaker TC (1994) STU1, a suppressor of a beta-tubulin mutation, encodes a novel and essential component of the yeast mitotic spindle. J Cell Biol 127(6 Pt 2):1973–1984

    Article  CAS  PubMed  Google Scholar 

  • Pearson CG, Bloom K (2004) Dynamic microtubules lead the way for spindle positioning. Nat Rev Mol Cell Biol 5(6):481–492

    Article  CAS  PubMed  Google Scholar 

  • Pellman D, Bagget M, Tu YH, Fink GR, Tu H (1995) Two microtubule-associated proteins required for anaphase spindle movement in Saccharomyces cerevisiae. J Cell Biol 130(6):1373–1385

    Article  CAS  PubMed  Google Scholar 

  • Pereira G, Schiebel E (2003) Separase regulates INCENP-Aurora B anaphase spindle function through Cdc14. Science 302:2120–2124

    Article  CAS  PubMed  Google Scholar 

  • Pereira G, Tanaka TU, Nasmyth K, Schiebel E (2001) Modes of spindle pole body inheritance and segregation of the Bfa1p–Bub2p checkpoint protein complex. EMBO J 20(22):6359–6370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raspelli E, Cassani C, Lucchini G, Fraschini R (2011) Budding yeast Dma1 and Dma2 participate in regulation of Swe1 levels and localization. Mol Biol Cell 22(13):2185–2197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raspelli E, Cassani C, Chiroli E, Fraschini R (2015) Budding yeast Swe1 is involved in the control of mitotic spindle elongation and is regulated by Cdc14 phosphatase during mitosis. J Biol Chem 290(1):1–12

    Article  CAS  PubMed  Google Scholar 

  • Rizk RS, DiScipio KA, Proudfoot KG, Gupta MR Jr (2014) The kinesin-8 Kip3 scales anaphase spindle length by suppression of midzone microtubule polymerization. J Cell Biol 204(6):965–975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roccuzzo M, Visintin C, Tili F, Visintin R (2015) FEAR-mediated activation of Cdc14 is the limiting step for spindle elongation and anaphase progression. Nat Cell Biol 17(3):251–261

    Article  CAS  PubMed  Google Scholar 

  • Rogers GC, Rogers SL, Sharp DJ (2005) Spindle microtubules in flux. J Cell Sci 118(Pt 6):1105–1116

    Article  CAS  PubMed  Google Scholar 

  • Roof DM, Meluh PB, Rose MD (1992) Kinesin-related proteins required for assembly of the mitotic spindle. J Cell Biol 118(1):95–108

    Article  CAS  PubMed  Google Scholar 

  • Rozelle DK, Hansen SD, Kaplan KB (2011) Chromosome passenger complexes control anaphase duration and spindle elongation via a kinesin-5 brake. J Cell Biol 193:285–294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saunders WS, Hoyt MA (1992) Kinesin-related proteins required for structural integrity of the mitotic spindle. Cell 70(3):451–458

    Article  CAS  PubMed  Google Scholar 

  • Schuyler SC, Liu JY, Pellman D (2003) The molecular function of Ase1p: evidence for a MAP-dependent midzone-specific spindle matrix. J Cell Biol 160(4):517–528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Segal M, Clarke DJ, Maddox P, Salmon ED, Bloom K, Reed SI (2000) Coordinated spindle assembly and orientation requires Clb5-dependent kinase in budding yeast. J Cell Biol 148:441–451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Severin F, Habermann B, Huffaker T, Hyman T (2001) Stu2 promotes mitotic spindle elongation in anaphase. J Cell Biol 153(2):435–442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stegmeier F, Amon A (2004) Closing mitosis: the functions of the Cdc14 phosphatase and its regulation. Annu Rev Genet 38:203–232

    Article  CAS  PubMed  Google Scholar 

  • Stegmeier F, Visintin R, Amon A (2002) Separase, polo kinase, the kinetochore protein Slk19, and Spo12 function in a network that controls Cdc14 localization during early anaphase. Cell 108(2):207–220

    Article  CAS  PubMed  Google Scholar 

  • Tirnauer JS, O’Toole E, Berrueta L, Bierer BE, Pellman D (1999) Yeast Bim1p promotes the G1-specific dynamics of microtubules. J Cell Biol 145:993–1007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vaisberg EA, Koonce MP, McIntosh JR (1993) Cytoplasmic dynein plays a role in mammalian mitotic spindle formation. J Cell Biol 123:849–858

    Article  CAS  PubMed  Google Scholar 

  • Varga V, Helenius J, Tanaka K, Hyman AA, Tanaka TU, Howard J (2006) Yeast kinesin-8 depolymerizes microtubules in a length-dependent manner. Nat Cell Biol 8(9):957–962

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Tsai JW, Imai JH, Lian WN, Vallee RB, Shi SH (2009) Asymmetric centrosome inheritance maintains neural progenitors in the neocortex. Nature 461(7266):947–955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wargacki MM, Tay JC, Muller EG, Asbury CL, Davis TN (2010) Kip3, the yeast kinesin-8, is required for clustering of kinetochores at metaphase. Cell Cycle 9(13):2581–2588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Waters JC, Mitchison TJ, Rieder CL, Salmon ED (1996) The kinetochore microtubule minus-end disassembly associated with poleward flux produces a force that can do work. Mol Biol Cell 7:1547–1558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Winey M, Bloom K (2012) Mitotic spindle form and function. Genetics 190(4):1197–1224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Winey M, Mamay CL, Toole ETO, Mastronarde DN, Giddings TH Jr, McDonald KL, McIntosh JR (1995) Three-dimensional ultrastructural analysis of the Saccharomyces cerevisiae mitotic spindle. J Cell Biol 129:1601–1615

    Article  CAS  PubMed  Google Scholar 

  • Woodbury EL, Morgan DO (2007) Cdk and APC activities limit the spindle-stabilizing function of Fin1 to anaphase. Nat Cell Biol 9(1):106–112

    Article  CAS  PubMed  Google Scholar 

  • Woodruff JB, Drubin DG, Barnes G (2010) Mitotic spindle disassembly occurs via distinct subprocesses driven by the anaphase-promoting complex, Aurora B kinase, and kinesin-8. J Cell Biol 191:795–808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woodruff JB, Drubin DG, Barnes G (2012) Spindle assembly requires complete disassembly of spindle remnants from the previous cell cycle. Mol Biol Cell 23(2):258–267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yeh E, Skibbens RV, Cheng JW, Salmon ED, Bloom K (1995) Spindle dynamics and cell cycle regulation of dynein in the budding yeast, Saccharomyces cerevisiae. J Cell Biol 130(3):687–700

    Article  CAS  PubMed  Google Scholar 

  • Yin H, You L, Pasqualone D, Kopski KM, Huffaker TC (2002) Stu1p is physically associated with beta-tubulin and is required for structural integrity of the mitotic spindle. Mol Biol Cell 13:1881–1892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

I would like to thank present and past members of RF’s lab for useful comments and discussions and an anonymous reviewer for helpful suggestions. RF’s research was supported by the Italian Ministry of University and Reasearch (PRIN – Progetti di Ricerca di Interesse Nazionale) and by the University of Milano Bicocca.

Statement

The authors declare that this manuscript has not been published elsewhere and it has not been submitted for publication elsewhere. All authors agree to the submission to the journal.

Compliance with Ethical Standards

Conflicts of interest The authors declare no conflicts of interest.

Ethical approval This article do not contain any studies with human participants or animals performed by any of the authors.

Author information

Authors and Affiliations

  1. Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Piazza della Scienza 2, 20126, Milan, Italy

    Roberta Fraschini

Authors
  1. Roberta Fraschini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roberta Fraschini .

Editor information

Editors and Affiliations

  1. Biochem and Mol Biol, Baylor College of Medicine, Houston, Texas, USA

    M. Zouhair Atassi

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Fraschini, R. (2016). Factors that Control Mitotic Spindle Dynamics. In: Atassi, M. (eds) Protein Reviews. Advances in Experimental Medicine and Biology(), vol 925. Springer, Singapore. https://doi.org/10.1007/5584_2016_74

Download citation

Publish with us

Policies and ethics

Search

Navigation