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Polo/PLK1 phosphorylation relieves Centrosomin (Cnn) autoinhibition to drive centrosome scaffold assembly

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.

INSTRUMENT(S):

ORGANISM(S): Drosophila Melanogaster (fruit Fly)

SUBMITTER: Marjorie Fournier

LAB HEAD: Jordan Raff

PROVIDER: PXD080319 | Pride | 2026-07-23

REPOSITORIES: Pride

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			Action	DRS
	220819_NM_PhosphoID_1FDR_Complex.xlsx	Xlsx
	220819_NM_PhosphoID_1FDR_Sample1.xlsx	Xlsx
	ASTZ_MF_260220_Neo_NM-229_048.raw	Raw
	ASTZ_MF_260220_Neo_NM-233_049.raw	Raw
	ASTZ_MF_260220_Neo_NM-nG-Spd5_050.raw	Raw

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