Regulation of minimal spindle midzone organization by mitotic kinases.
Spindle Apparatus
/ metabolism
Phosphorylation
Humans
CDC2 Protein Kinase
/ metabolism
Protein Serine-Threonine Kinases
/ metabolism
Cell Cycle Proteins
/ metabolism
Microtubules
/ metabolism
Kinesins
/ metabolism
Polo-Like Kinase 1
Proto-Oncogene Proteins
/ metabolism
Mitosis
Anaphase
HeLa Cells
Metaphase
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
29 Oct 2024
29 Oct 2024
Historique:
received:
20
02
2024
accepted:
11
10
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
During cell division, the microtubule cytoskeleton undergoes dramatic cell cycle-driven reorganizations of its architecture. Coordinated by changes in the phosphorylation patterns of a multitude of microtubule associated proteins, the mitotic spindle first self-assembles to capture the chromosomes and then reorganizes in anaphase as the chromosomes are segregated. A key protein for this reorganization is PRC1 which is differentially phosphorylated by the mitotic kinases CDK1 and PLK1. How the phosphorylation state of PRC1 orchestrates spindle reorganization is not understood mechanistically. Here, we reconstitute in vitro the transition between metaphase and anaphase-like microtubule architectures triggered by the changes in PRC1 phosphorylation. We find that whereas PLK1 regulates its own recruitment by PRC1, CDK1 controls the affinity of PRC1 for antiparallel microtubule binding. Dephosphorylation of CDK1-phosphorylated PRC1 is required and sufficient to trigger the reorganization of a minimal anaphase midzone in the presence of the midzone length controlling kinesin KIF4A. These results demonstrate how phosphorylation-controlled affinity changes regulate the architecture of active microtubule networks, providing new insight into the mechanistic underpinnings of the cell cycle-driven reorganization of the central spindle during mitosis.
Identifiants
pubmed: 39472429
doi: 10.1038/s41467-024-53500-1
pii: 10.1038/s41467-024-53500-1
doi:
Substances chimiques
CDC2 Protein Kinase
EC 2.7.11.22
Protein Serine-Threonine Kinases
EC 2.7.11.1
Cell Cycle Proteins
0
Kinesins
EC 3.6.4.4
Polo-Like Kinase 1
0
Proto-Oncogene Proteins
0
KIF4A protein, human
EC 3.6.1.-
PRC1 protein, human
0
CDK1 protein, human
EC 2.7.11.22
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9213Subventions
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : 951430
Organisme : Human Frontier Science Program (HFSP)
ID : HFSP LT000682/2020-C
Informations de copyright
© 2024. The Author(s).
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