Kinetochore function is controlled by a phospho-dependent coexpansion of inner and outer components

The Journal of Cell Biology
David J Wynne, Hironori Funabiki

Abstract

It is widely accepted that the kinetochore is built on CENP-A-marked centromeric chromatin in a hierarchical order from inner to outer kinetochore. Recruitment of many kinetochore proteins depends on microtubule attachment status, but it remains unclear how their assembly/disassembly is orchestrated. Applying 3D structured illumination microscopy to Xenopus laevis egg extracts, here we reveal that in the absence of microtubule attachment, proteins responsible for lateral attachment and spindle checkpoint signaling expand to form micrometer-scale fibrous structures over CENP-A-free chromatin, whereas a core module responsible for end-on attachment (CENP-A, CENP-T, and Ndc80) does not. Both outer kinetochore proteins (Bub1, BubR1, Mad1, and CENP-E) and the inner kinetochore component CENP-C are integral components of the expandable module, whose assembly depends on multiple mitotic kinases (Aurora B, Mps1, and Plx1) and is suppressed by protein phosphatase 1. We propose that phospho-dependent coexpansion of CENP-C and outer kinetochore proteins promotes checkpoint signal amplification and lateral attachment, whereas their selective disassembly enables the transition to end-on attachment.

References

Jan 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·K HaraM Kirschner
Jan 1, 1996·Cell Motility and the Cytoskeleton·D A ThrowerL Wilson
Apr 1, 1997·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·K SugimotoM Himeno
Oct 24, 1998·The Journal of Cell Biology·R H ChenA W Murray
Jun 9, 2004·Current Biology : CB·Bonnie J HowellE D Salmon
Jul 23, 2004·Molecular Biology of the Cell·Suzanne VigneronThierry Lorca
Sep 17, 2004·Molecular Biology of the Cell·Jeffrey H Stear, Mark B Roth
Sep 8, 2005·The Journal of Cell Biology·Yinghui MaoDon W Cleveland
Jan 21, 2006·Science·Tarun M KapoorAlexey Khodjakov
Mar 23, 2007·The Journal of Biological Chemistry·Shigeru MatsumuraEisuke Nishida
Mar 29, 2007·The Journal of Cell Biology·Yekaterina BoyarchukAlexei Arnaoutov
Nov 30, 2007·Molecular Biology of the Cell·Iain M CheesemanArshad Desai
Dec 21, 2007·Molecular Biology of the Cell·Tetsuya HoriTatsuo Fukagawa

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Citations

Feb 3, 2016·The Journal of Cell Biology·Valentin MagidsonAlexey Khodjakov
Mar 8, 2016·Current Opinion in Cell Biology·Banafsheh Etemad, Geert J P L Kops
Dec 17, 2015·The Journal of Cell Biology·Rebecca Heald, Alexey Khodjakov
Jul 5, 2016·Chromosoma·Harsh Nagpal, Tatsuo Fukagawa
Sep 4, 2016·ELife·Chris A SmithNigel J Burroughs
Nov 5, 2016·Molecular Biology of the Cell·Pavithra AravamudhanAjit P Joglekar
Jan 27, 2017·PloS One·Nicole J CamlinJanet E Holt
Jan 27, 2017·Biology·Andrea Musacchio, Arshad Desai
Feb 9, 2017·Journal of Pineal Research·Mianqun ZhangBo Xiong
Jun 16, 2016·F1000Research·Eric A SheldenJonathan C R Jones
May 24, 2019·The Journal of Cell Biology·Karthik DhatchinamoorthyJennifer L Gerton
Nov 26, 2019·Biotechnic & Histochemistry : Official Publication of the Biological Stain Commission·Qilun YaoWenbo Li
Mar 25, 2020·The Journal of Cell Biology·Philip AucklandAndrew D McAinsh
Mar 24, 2020·The EMBO Journal·Lindsey A AllanAdrian T Saurin
Feb 14, 2020·Cellular and Molecular Life Sciences : CMLS·Masatoshi Hara, Tatsuo Fukagawa
Sep 15, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Mianqun ZhangBo Xiong
Aug 16, 2018·Science Signaling·Vladimir Joukov, Arcangela De Nicolo
Mar 23, 2017·The Journal of Cell Biology·Shyamal MosalagantiAndrea Musacchio
Mar 23, 2017·The Journal of Cell Biology·José B GamaReto Gassmann
Aug 20, 2017·Scientific Reports·Masanori Ikeda, Kozo Tanaka
Mar 8, 2017·Proceedings of the National Academy of Sciences of the United States of America·Giulia VargiuWilliam C Earnshaw
Jan 10, 2017·Biology·Michael A Lampson, Ekaterina L Grishchuk
Jul 5, 2018·Frontiers in Cell and Developmental Biology·Adrian T Saurin
Aug 18, 2018·Journal of Cell Science·Julie K Monda, Iain M Cheeseman
Jul 16, 2019·Cell Systems·Jesse C PattersonMichael B Yaffe
May 1, 2018·Current Biology : CB·Danica DrpicHelder Maiato
Oct 10, 2020·Current Biology : CB·Alexander A KukrejaAjit P Joglekar
May 28, 2019·Current Opinion in Cell Biology·Alexandra F LongSophie Dumont
Apr 11, 2021·Seminars in Cell & Developmental Biology·Fioranna Renda, Alexey Khodjakov

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Methods Mentioned

BETA
electron microscopy
fluorescence microscopy
immunodepletion
Infrared Imaging

Software Mentioned

MathWorks
softWoRx
Imaris
MATLAB
ImageJ

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