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Cited by 12Microtubule 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 PI·2023·The EMBO Journal
DOI 10.15252/embj.2023113647PMC PMC10620760

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Abstract

During mitosis, spindle architecture alters as chromosomes segregate into daughter cells. The microtubule crosslinker protein regulator of 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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Metadata

Authors
Gluszek‐Kustusz, A., Craske, B., Legal, T., McHugh, T., & Welburn, J. P.
Affiliations
Wellcome Centre for Cell Biology (GB)
Corresponding author
Welburn, Julie PI
ORCID
Venue
The EMBO Journal
Publisher
Springer Science and Business Media LLC
Published
2023-08-18
Volume
42
Issue
21
Pages
e113647-e113647
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
DOI
10.15252/embj.2023113647
PMC
PMC10620760
OpenAlex
W4385969735
Cited by
12
References
3
Citations by year
2026: 2 · 2025: 5 · 2024: 4 · 2023: 1
FWCI
1.74
Type
journal article
Language
en
Open access
Licence
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
  • Royal Society of Edinburgh
  • UKRI | Biotechnology and Biological Sciences Research Council (BB/M010996/1)
  • Wellcome Trust (207430, 203149, 101527)
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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