Polo/PLK1 phosphorylation relieves Centrosomin/Cnn autoinhibition to promote centrosome scaffold assembly

Mitotic centrosome maturation requires Polo/PLK1-dependent expansion of the pericentriolar material (PCM). In Drosophila, Centrosomin (Cnn) assembles a scaffold around mitotic centrioles through interactions between its PReM and CM2 domains. Here, we show that PReM adopts an autoinhibited helical hairpin conformation that prevents CM2 binding. Polo/PLK1 phosphorylation relieves this autoinhibition, enabling scaffold assembly, whereas phospho-blocking mutations disrupt PReM-CM2 binding in vitro and Cnn scaffold assembly in vivo. Potential functionally analogous domains have been identified in the human and C. elegans Cnn homologues CDK5RAP2 and SPD-5. We find that the human protein appears to share a structurally similar mechanism for scaffold assembly, but the worm protein does not. Consistent with this, deletion of these domains alters the dynamics of Cnn condensates in vitro, but has little effect on SPD-5 condensate dynamics. We conclude that Polo/PLK1 promotes mitotic centrosome assembly, at least in part, by relieving autoinhibitory intramolecular interactions.

Authors

Institutions

Publication Details

Journal
The EMBO Journal
Published
2026-07-30
DOI
https://doi.org/10.1038/s44318-026-00878-x
Primary Topic
Microtubule and mitosis dynamics
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Polo/PLK1 phosphorylation relieves Centrosomin/Cnn autoinhibition to promote centrosome scaffold assembly

Anna Caballe, Jordan W. Raff, Martine Ruer, Andrey Pozniakovsky et al.
The EMBO Journal
Microtubule and mitosis dynamics
article

Polo/PLK1 phosphorylation relieves Centrosomin/Cnn autoinhibition to promote centrosome scaffold assembly

Anna Caballe, Jordan W. Raff, Martine Ruer, Andrey Pozniakovsky, Alan Wainman, Anupa Majumdar, Siu‐Shing Wong, Anthony A. Hyman, Steven Johnson, Nada Mohamad, Lars Hubatsch, Susan M. Lea, Ingelise Holland-Kaye, Andreas F M Haensele, Zsofia Novak
article en

Abstract

Mitotic centrosome maturation requires Polo/PLK1-dependent expansion of the pericentriolar material (PCM). In Drosophila, Centrosomin (Cnn) assembles a scaffold around mitotic centrioles through interactions between its PReM and CM2 domains. Here, we show that PReM adopts an autoinhibited helical hairpin conformation that prevents CM2 binding. Polo/PLK1 phosphorylation relieves this autoinhibition, enabling scaffold assembly, whereas phospho-blocking mutations disrupt PReM-CM2 binding in vitro and Cnn scaffold assembly in vivo. Potential functionally analogous domains have been identified in the human and C. elegans Cnn homologues CDK5RAP2 and SPD-5. We find that the human protein appears to share a structurally similar mechanism for scaffold assembly, but the worm protein does not. Consistent with this, deletion of these domains alters the dynamics of Cnn condensates in vitro, but has little effect on SPD-5 condensate dynamics. We conclude that Polo/PLK1 promotes mitotic centrosome assembly, at least in part, by relieving autoinhibitory intramolecular interactions.

The EMBO Journal
St. Jude Children's Research Hospital (US), University of Oxford (GB), Max Planck Institute of Molecular Cell Biology and Genetics (DE)
Wellcome Trust, Cancer Research UK, Croucher Foundation, Balliol College, University of Oxford, Clarendon Fund
Openalex Percentile: Top 13%
Microtubule and mitosis dynamics
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.