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PreprintCited by 11Microtubule and mitosis dynamicsGenomics and Chromatin DynamicsDNA Repair Mechanisms

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Phosphorylation controls spatial and temporal activities of motor-PRC1 complexes to complete mitosis

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Gluszek-Kustusz, Agata, Craske, Benjamin, Legal, Thibault, McHugh, Toni, Welburn, Julie P.I.·2023·The EMBO Journal
DOI 10.1101/2023.03.11.531660PMC PMC10620760

Preprint — published as 10.15252/embj.2023113647 · Paper page

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Abstract

During mitosis, spindle architecture alters as chromosomes segregate to daughter cells. The microtubule crosslinker Protein Required for Cytokinesis 1 (PRC1) is essential for spindle stability, chromosome segregation and completion of cytokinesis, but how it recruits motors to the central spindle to coordinate the segregation of chromosomes is unknown. Here, we combine structural and cell biology approaches to show that the human CENP-E motor, which is essential for chromosome capture and alignment by microtubules, binds to PRC1 through a conserved hydrophobic motif. This binding mechanism is also used by Kinesin-4 Kif4A:PRC1. Using in vitro reconstitution, we demonstrate that CENP-E slides antiparallel PRC1-crosslinked microtubules. We find that the regulation of CENP-E -PRC1 interaction is spatially and temporally coupled with relocalization to overlapping microtubules in anaphase. Finally, we demonstrate that the PRC1:microtubule motor interaction is essential in anaphase to control chromosome partitioning, retain central spindle integrity and ensure cytokinesis. Taken together our findings reveal the molecular basis for the cell cycle regulation of motor-PRC1 complexes to couple chromosome segregation and cytokinesis.

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Research works printed but not linked: 63

  1. 10.1016/j.cub.2020.04.081 · DOI
  2. 10.1038/nmeth.1896 · DOI · Paper page
  3. 10.1016/j.cell.2010.06.033 · DOI · Paper page
  4. 10.1038/nchembio.2495 · DOI
  5. 10.1091/mbc.E08-09-0971 · DOI · Paper page
  6. 2022, Coupling of microtubule bundles isolates them from local disruptions to set the structural stability of the anaphase spindle, Proc Natl Acad Sci U S A, 119, e2204068119, 10.1073/pnas.2204068119 · DOI
  7. 10.1083/jcb.146.5.941 · DOI
  8. 10.1083/jcb.143.1.49 · DOI
  9. 2005, A combined approach for the localization and tandem affinity purification of protein complexes from metazoans, Sci STKE, 2005, l1
  10. 10.1074/jbc.RA118.003154 · DOI
  11. 10.1007/s004120050266 · DOI
  12. 2022, Reconstitution of an active human CENP-E motor, Open Biol, 12, 210389, 10.1098/rsob.210389 · DOI
  13. 10.1073/pnas.0805139105 · DOI · Paper page
  14. 10.1016/j.semcdb.2010.08.005 · DOI · Paper page
  15. 10.1016/j.cell.2014.02.018 · DOI
  16. 2020, The Mitotic Crosslinking Protein PRC1 Acts Like a Mechanical Dashpot to Resist Microtubule Sliding, Dev Cell, 54, 367, 10.1016/j.devcel.2020.06.017 · DOI
  17. 10.1038/nrm2609 · DOI
  18. 10.1083/jcb.200403084 · DOI
  19. 10.1083/jcb.200511061 · DOI
  20. 10.1038/ncb2831 · DOI
  21. 10.1016/j.cub.2019.05.049 · DOI
  22. 10.1016/j.semcdb.2010.01.017 · DOI
  23. 10.1091/mbc.E12-01-0058 · DOI
  24. 10.1016/j.cell.2010.12.001 · DOI · Paper page
  25. 10.1016/j.cell.2006.12.030 · DOI
  26. 10.1016/S1097-2765(00)80302-0 · DOI
  27. 10.1038/ncomms10298 · DOI
  28. 10.1126/scisignal.2001497 · DOI
  29. 10.1371/journal.pone.0064826 · DOI
  30. 10.1038/sj.emboj.7600347 · DOI · Paper page
  31. 10.1038/ncomms8290 · DOI
  32. Legal, T. , D. Hayward , A. Gluszek-Kustusz , E.A. Blackburn , C. Spanos , J. Rappsilber , U. Gruneberg , and J.P.I. Welburn . 2020. The C-terminal helix of BubR1 is essential for CENP-E-dependent chromosome alignment. J Cell Sci. 133. · DOI
  33. 10.1038/s41568-018-0084-6 · DOI
  34. 2020, Mitotic motor CENP-E cooperates with PRC1 in temporal control of central spindle assembly, J Mol Cell Biol, 12, 654, 10.1093/jmcb/mjz051 · DOI
  35. 10.1021/pr9003773 · DOI
  36. McHugh, T. , A.A. Gluszek , and J.P.I. Welburn . 2018. Microtubule end tethering of a processive kinesin-8 motor Kif18b is required for spindle positioning. J Cell Biol. · DOI
  37. 10.18632/oncotarget.13556 · DOI
  38. 10.1016/j.devcel.2017.01.012 · DOI
  39. 2022, ColabFold: making protein folding accessible to all, Nat Methods, 19, 679, 10.1038/s41592-022-01488-1 · DOI · Paper page
  40. 10.1083/jcb.200111052 · DOI
  41. 10.1091/mbc.E04-04-0346 · DOI
  42. 10.1073/pnas.0507066103 · DOI
  43. 2016, Motor activity of centromere-associated protein-E contributes to its localization at the center of the midbody to regulate cytokinetic abscission, Oncotarget, 7, 79964, 10.18632/oncotarget.13206 · DOI
  44. 10.1126/scisignal.2000475 · DOI
  45. 10.1083/jcb.201904169 · DOI
  46. Poser, E. , R. Caous , U. Gruneberg , and F.A. Barr . 2019. Aurora A promotes chromosome congression by activating the condensin-dependent pool of KIF4A. J Cell Biol. 219. · DOI
  47. 2010, Discovery of the First Potent and Selective Inhibitor of Centromere-Associated Protein E: GSK923295, ACS medicinal chemistry letters, 1, 30, 10.1021/ml900018m · DOI
  48. 10.1016/j.cub.2021.03.082 · DOI
  49. 10.1083/jcb.201202155 · DOI
  50. 2011, The Plk1-dependent phosphoproteome of the early mitotic spindle, Mol Cell Proteomics, 10, 004457
  51. 10.1083/jcb.139.6.1373 · DOI
  52. 10.1038/nmeth.2089 · DOI · Paper page
  53. Serena, M. , R.N. Bastos , P.R. Elliott , and F.A. Barr . 2020. Molecular basis of MKLP2-dependent Aurora B transport from chromatin to the anaphase central spindle. J Cell Biol. 219. · DOI
  54. 10.1016/j.celrep.2014.07.036 · DOI
  55. 2020, Microtubule poleward flux in human cells is driven by the coordinated action of four kinesins, EMBO J, 39, e105432, 10.15252/embj.2020105432 · DOI
  56. 10.1016/j.cell.2013.06.021 · DOI
  57. 10.1016/j.cell.2010.07.012 · DOI
  58. 10.1016/j.devcel.2021.04.005 · DOI
  59. 10.1083/jcb.128.5.761 · DOI
  60. Wijeratne, S. , and R. Subramanian . 2018. Geometry of antiparallel microtubule bundles regulates relative sliding and stalling by PRC1 and Kif4A. Elife. 7. · DOI
  61. 10.1083/jcb.139.2.435 · DOI
  62. 10.1002/j.1460-2075.1991.tb08066.x · DOI
  63. 10.1073/pnas.0408438102 · DOI

Metadata

Authors
Gluszek-Kustusz, A., Craske, B., Legal, T., McHugh, T., & Welburn, J. P. I.
Affiliations
Wellcome Centre for Cell Biology (GB)
Corresponding author
Welburn, Julie P.I.
ORCID
Venue
The EMBO Journal
Publisher
openRxiv
Published
2023-03-11
Volume
42
Issue
21
Pages
e113647-e113647
ISSN
0261-4189 (ISSN-L)
DOI
10.1101/2023.03.11.531660
PMC
PMC10620760
OpenAlex
W4385969735
Cited by
11
References
1
Citations by year
2026: 2 · 2025: 5 · 2024: 4
FWCI
1.58
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • The EMBO Journal (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (101527, 207430/Z/17/Z, 207430, 203149)
  • Royal Society
  • Royal Society of Edinburgh
  • Directorate for Biological Sciences
  • Biotechnology and Biological Sciences Research Council (BB/M010996/1, M010996, M010996/1, 1868240, 203149)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords
PRC1, CENP-E, kinesin-4, KIF4A, microtubule motor proteins, phosphorylation, central spindle, chromosome segregation, cytokinesis, anaphase, microtubule sliding, hydrophobic motif, mitosis, spindle stability
MeSH terms
Humans, Microtubules, Mitosis, Spindle Apparatus, Phosphorylation, Kinesins, Cell Cycle Proteins, Cytokinesis

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