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Article Dans Une Revue Journal of Cell Biology Année : 2021

Autoinhibition of Cnn binding to γ-TuRCs prevents ectopic microtubule nucleation and cell division defects

Chisato Tsuji
Alice Egerton
Antoine Guichet
Marc de La Roche

Résumé

γ-Tubulin ring complexes (γ-TuRCs) nucleate microtubules. They are recruited to centrosomes in dividing cells via binding to N-terminal CM1 domains within γ-TuRC–tethering proteins, including Drosophila Centrosomin (Cnn). Binding promotes microtubule nucleation and is restricted to centrosomes in dividing cells, but the mechanism regulating binding remains unknown. Here, we identify an extreme N-terminal CM1 autoinhibition (CAI) domain found specifically within the centrosomal isoform of Cnn (Cnn-C) that inhibits γ-TuRC binding. Robust binding occurs after removal of the CAI domain or with the addition of phosphomimetic mutations, suggesting that phosphorylation helps relieve inhibition. We show that regulation of Cnn binding to γ-TuRCs is isoform specific and that misregulation of binding can result in ectopic cytosolic microtubules and major defects during cell division. We also find that human CDK5RAP2 is autoinhibited from binding γ-TuRCs, suggesting conservation across species. Overall, our results shed light on how and why CM1 domain binding to γ-TuRCs is regulated.
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Dates et versions

hal-03365863 , version 1 (05-10-2021)

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Corinne Tovey, Chisato Tsuji, Alice Egerton, Fred Bernard, Antoine Guichet, et al.. Autoinhibition of Cnn binding to γ-TuRCs prevents ectopic microtubule nucleation and cell division defects. Journal of Cell Biology, 2021, 220 (8), ⟨10.1083/jcb.202010020⟩. ⟨hal-03365863⟩

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