Lateral to End-on Conversion of Chromosome-microtubule Attachment Requires Kinesins CENP-E and MCAK

Overview

Journal Curr Biol

Publisher Cell Press

Specialty Biology

Date 2013 Jul 30

PMID 23891108

Citations 79

Authors

Roshan L Shrestha

Viji M Draviam

Affiliations

Soon will be listed here.

Abstract

Background: Proper attachment of chromosomes to microtubules is crucial for the accurate segregation of chromosomes. Human chromosomes attach initially to lateral walls of microtubules. Subsequently, attachments to lateral walls disappear and attachments to microtubule ends (end-on attachments) predominate. While it is known in yeasts that lateral to end-on conversion of attachments occurs through a multistep process, equivalent conversion steps in humans remain unknown.

Results: By developing a high-resolution imaging assay to visualize intermediary steps of the lateral to end-on conversion process, we show that the mechanisms that bring a laterally bound chromosome and its microtubule end closer to each other are indispensable for proper end-on attachment because laterally attached chromosomes seldom detach. We show that end-on conversion requires (1) the plus-end-directed motor CENP-E to tether the lateral kinetochore onto microtubule walls and (2) the microtubule depolymerizer MCAK to release laterally attached microtubules after a partial end-on attachment is formed.

Conclusions: By uncovering a CENP-E mediated wall-tethering event and a MCAK-mediated wall-removing event, we establish that human chromosome-microtubule attachment is achieved through a set of deterministic sequential events rather than stochastic direct capture of microtubule ends.

Citing Articles

MCAK/Kif2C centromeric activity level tunes K-fiber stability.

Wordeman L, Wagenbach M, Vicente J bioRxiv. 2025; .

PMID: 40027728 PMC: 11870468. DOI: 10.1101/2025.02.16.638494.

CENcyclopedia: Dynamic Landscape of Kinetochore Architecture Throughout the Cell Cycle.

Chen Y, Kilic E, Wang E, Rossman W, Suzuki A bioRxiv. 2024; .

PMID: 39677682 PMC: 11643120. DOI: 10.1101/2024.12.05.627000.

Fibrous corona is reduced in cancer cell lines that attenuate microtubule nucleation from kinetochores.

Ishikawa Y, Fukue H, Iwakami R, Ikeda M, Iemura K, Tanaka K Cancer Sci. 2024; 116(2):420-431.

PMID: 39604214 PMC: 11786318. DOI: 10.1111/cas.16406.

A kinetochore-associated kinesin-7 motor cooperates with BUB3.3 to regulate mitotic chromosome congression in Arabidopsis thaliana.

Tang X, He Y, Tang Y, Chen K, Lin H, Liu B Nat Plants. 2024; 10(11):1724-1736.

PMID: 39414927 DOI: 10.1038/s41477-024-01824-7.

Kinesin-7 CENP-E mediates centrosome organization and spindle assembly to regulate chromosome alignment and genome stability.

Chen J, Wu S, He J, Liu Y, Deng Z, Fang H Cell Prolif. 2024; 58(1):e13745.

PMID: 39266203 PMC: 11693568. DOI: 10.1111/cpr.13745.

References

Cai S, OConnell C, Khodjakov A, Walczak C . Chromosome congression in the absence of kinetochore fibres. Nat Cell Biol. 2009; 11(7):832-8. PMC: 2895821. DOI: 10.1038/ncb1890. View

Meraldi P, Sorger P . A dual role for Bub1 in the spindle checkpoint and chromosome congression. EMBO J. 2005; 24(8):1621-33. PMC: 1142573. DOI: 10.1038/sj.emboj.7600641. View

Jaqaman K, King E, Amaro A, Winter J, Dorn J, Elliott H . Kinetochore alignment within the metaphase plate is regulated by centromere stiffness and microtubule depolymerases. J Cell Biol. 2010; 188(5):665-79. PMC: 2835940. DOI: 10.1083/jcb.200909005. View

Yao X, Abrieu A, Zheng Y, Sullivan K, Cleveland D . CENP-E forms a link between attachment of spindle microtubules to kinetochores and the mitotic checkpoint. Nat Cell Biol. 2000; 2(8):484-91. DOI: 10.1038/35019518. View

Wordeman L, Wagenbach M, von Dassow G . MCAK facilitates chromosome movement by promoting kinetochore microtubule turnover. J Cell Biol. 2007; 179(5):869-79. PMC: 2099197. DOI: 10.1083/jcb.200707120. View

Dong Y, Vanden Beldt K, Meng X, Khodjakov A, McEwen B . The outer plate in vertebrate kinetochores is a flexible network with multiple microtubule interactions. Nat Cell Biol. 2007; 9(5):516-22. PMC: 2895818. DOI: 10.1038/ncb1576. View

Schaar B, Chan G, Maddox P, Salmon E, Yen T . CENP-E function at kinetochores is essential for chromosome alignment. J Cell Biol. 1998; 139(6):1373-82. PMC: 2132614. DOI: 10.1083/jcb.139.6.1373. View

McEwen B, Heagle A, Cassels G, Buttle K, Rieder C . Kinetochore fiber maturation in PtK1 cells and its implications for the mechanisms of chromosome congression and anaphase onset. J Cell Biol. 1997; 137(7):1567-80. PMC: 2137823. DOI: 10.1083/jcb.137.7.1567. View

Yeh T, Kowalska A, Scipioni B, Cheong F, Zheng M, Derewenda U . Dynactin helps target Polo-like kinase 1 to kinetochores via its left-handed beta-helical p27 subunit. EMBO J. 2013; 32(7):1023-35. PMC: 3616283. DOI: 10.1038/emboj.2013.30. View

10.

Kline S, Cheeseman I, Hori T, Fukagawa T, Desai A . The human Mis12 complex is required for kinetochore assembly and proper chromosome segregation. J Cell Biol. 2006; 173(1):9-17. PMC: 2063780. DOI: 10.1083/jcb.200509158. View

11.

Bakhoum S, Thompson S, Manning A, Compton D . Genome stability is ensured by temporal control of kinetochore-microtubule dynamics. Nat Cell Biol. 2008; 11(1):27-35. PMC: 2614462. DOI: 10.1038/ncb1809. View

12.

Domnitz S, Wagenbach M, Decarreau J, Wordeman L . MCAK activity at microtubule tips regulates spindle microtubule length to promote robust kinetochore attachment. J Cell Biol. 2012; 197(2):231-7. PMC: 3328376. DOI: 10.1083/jcb.201108147. View

13.

Yao X, Anderson K, Cleveland D . The microtubule-dependent motor centromere-associated protein E (CENP-E) is an integral component of kinetochore corona fibers that link centromeres to spindle microtubules. J Cell Biol. 1997; 139(2):435-47. PMC: 2139792. DOI: 10.1083/jcb.139.2.435. View

14.

Ohi R, Coughlin M, Lane W, Mitchison T . An inner centromere protein that stimulates the microtubule depolymerizing activity of a KinI kinesin. Dev Cell. 2003; 5(2):309-21. DOI: 10.1016/s1534-5807(03)00229-6. View

15.

Zhang G, Kelstrup C, Hu X, Kaas Hansen M, Singleton M, Olsen J . The Ndc80 internal loop is required for recruitment of the Ska complex to establish end-on microtubule attachment to kinetochores. J Cell Sci. 2012; 125(Pt 13):3243-53. DOI: 10.1242/jcs.104208. View

16.

Kapoor T, Lampson M, Hergert P, Cameron L, Cimini D, Salmon E . Chromosomes can congress to the metaphase plate before biorientation. Science. 2006; 311(5759):388-91. PMC: 4768465. DOI: 10.1126/science.1122142. View

17.

Desai A, Verma S, Mitchison T, Walczak C . Kin I kinesins are microtubule-destabilizing enzymes. Cell. 1999; 96(1):69-78. DOI: 10.1016/s0092-8674(00)80960-5. View

18.

Schmidt J, Kiyomitsu T, Hori T, Backer C, Fukagawa T, Cheeseman I . Aurora B kinase controls the targeting of the Astrin-SKAP complex to bioriented kinetochores. J Cell Biol. 2010; 191(2):269-80. PMC: 2958477. DOI: 10.1083/jcb.201006129. View

19.

Magidson V, OConnell C, Loncarek J, Paul R, Mogilner A, Khodjakov A . The spatial arrangement of chromosomes during prometaphase facilitates spindle assembly. Cell. 2011; 146(4):555-67. PMC: 3291198. DOI: 10.1016/j.cell.2011.07.012. View

20.

Manning A, Bakhoum S, Maffini S, Correia-Melo C, Maiato H, Compton D . CLASP1, astrin and Kif2b form a molecular switch that regulates kinetochore-microtubule dynamics to promote mitotic progression and fidelity. EMBO J. 2010; 29(20):3531-43. PMC: 2964175. DOI: 10.1038/emboj.2010.230. View