Microtubule end conversion mediated by motors and diffusing proteins with no intrinsic microtubule end-binding activity

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作者
Manas Chakraborty
Ekaterina V. Tarasovetc
Anatoly V. Zaytsev
Maxim Godzi
Ana C. Figueiredo
Fazly I. Ataullakhanov
Ekaterina L. Grishchuk
机构
[1] University of Pennsylvania,Department of Physiology, Perelman School of Medicine
[2] Russian Academy of Sciences,Center for Theoretical Problems of Physicochemical Pharmacology
[3] Universidade do Porto,Chromosome Instability & Dynamics Laboratory, Instituto de Biologia Molecular e Celular
[4] Universidade do Porto,Instituto de Investigação e Inovação em Saúde – i3S
[5] Dmitry Rogachev National Research Center of Pediatric Hematology,Centre for Mechanochemical Cell Biology
[6] Oncology and Immunology,undefined
[7] Moscow Institute of Physics and Technology,undefined
[8] Warwick Medical School,undefined
来源
Nature Communications | / 10卷
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摘要
Accurate chromosome segregation relies on microtubule end conversion, the ill-understood ability of kinetochores to transit from lateral microtubule attachment to durable association with dynamic microtubule plus-ends. The molecular requirements for this conversion and the underlying biophysical mechanisms are elusive. We reconstituted end conversion in vitro using two kinetochore components: the plus end–directed kinesin CENP-E and microtubule-binding Ndc80 complex, combined on the surface of a microbead. The primary role of CENP-E is to ensure close proximity between Ndc80 complexes and the microtubule plus-end, whereas Ndc80 complexes provide lasting microtubule association by diffusing on the microtubule wall near its tip. Together, these proteins mediate robust plus-end coupling during several rounds of microtubule dynamics, in the absence of any specialized tip-binding or regulatory proteins. Using a Brownian dynamics model, we show that end conversion is an emergent property of multimolecular ensembles of microtubule wall-binding proteins with finely tuned force-dependent motility characteristics.
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[1]  
Walczak CE(2010)Mechanisms of chromosome behaviour during mitosis Nat. Rev. Mol. Cell Biol. 11 91-102
[2]  
Cai S(1997)CENP-E is a plus end-directed kinetochore motor required for metaphase chromosome alignment Cell 91 357-366
[3]  
Khodjakov A(1991)CENP-E, a novel human centromere-associated protein required for progression from metaphase to anaphase EMBO J. 10 1245-1254
[4]  
Wood KW(2002)Chromosome-microtubule interactions during mitosis Annu. Rev. Cell Dev. Biol. 18 193-219
[5]  
Sakowicz R(2012)Dynamic regulation of kinetochore-microtubule interaction during mitosis J. Biochem. 152 415-424
[6]  
Goldstein LSB(2018)Microtubules assemble near most kinetochores during early prometaphase in human cells J. Cell Biol. 217 2647-2659
[7]  
Cleveland DW(1998)The vertebrate cell kinetochore and its roles during mitosis Trends Cell Biol. 8 310-318
[8]  
Yen TJ(2013)Lateral to end-on conversion of chromosome-microtubule attachment requires kinesins cenp-e and MCAK Curr. Biol. 23 1514-1526
[9]  
McIntosh JR(2015)Regulation of kinetochore-microtubule attachments through homeostatic control during mitosis Nat. Rev. Mol. Cell Biol. 16 57-64
[10]  
Grishchuk EL(2017)Biophysics of microtubule end coupling at the kinetochore Prog. Mol. Subcell. Biol. 56 397-428