Phosphorylation Controls Spatial and Temporal activities of Motor-PRC1 Complexes to Complete Mitosis

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2023 Aug 18

PMID 37592895

Authors

Agata Gluszek-Kustusz

Benjamin Craske

Thibault Legal

Toni McHugh

Julie Pi Welburn

Affiliations

Soon will be listed here.

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

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