Regulation of minimal spindle midzone organization by mitotic kinases

Lim, Wei Ming; Chew, Wei-Xiang; Esposito Verza, Arianna; Pesenti, Marion; Musacchio, Andrea; Surrey, Thomas

doi:http://dx.doi.org/10.1038/s41467-024-53500-1

Regulation of minimal spindle midzone organization by mitotic kinases

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Lim WM, Chew WX, Esposito Verza A, Pesenti M, Musacchio A, Surrey T. Regulation of minimal spindle midzone organization by mitotic kinases. Nat Commun. 2024 Oct 29;15(1):9213. DOI: 10.1038/s41467-024-53500-1

Abstract

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.