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Autoinhibitory mechanism controls binding of centrosomin motif 1 to γ-tubulin ring complex

The γ-tubulin ring complex (γTuRC) is the principal nucleator of cellular microtubules, and the microtubule-nucleating activity of the complex is stimulated by binding to the γTuRC-mediated nucleation activator (γTuNA) motif. The γTuNA is part of the centrosomin motif 1 (CM1), which is widely found...

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Autores principales: Yang, Shaozhong, Au, Franco K.C., Li, Gefei, Lin, Jianwei, Li, Xiang David, Qi, Robert Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202828/
https://www.ncbi.nlm.nih.gov/pubmed/37213089
http://dx.doi.org/10.1083/jcb.202007101
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author Yang, Shaozhong
Au, Franco K.C.
Li, Gefei
Lin, Jianwei
Li, Xiang David
Qi, Robert Z.
author_facet Yang, Shaozhong
Au, Franco K.C.
Li, Gefei
Lin, Jianwei
Li, Xiang David
Qi, Robert Z.
author_sort Yang, Shaozhong
collection PubMed
description The γ-tubulin ring complex (γTuRC) is the principal nucleator of cellular microtubules, and the microtubule-nucleating activity of the complex is stimulated by binding to the γTuRC-mediated nucleation activator (γTuNA) motif. The γTuNA is part of the centrosomin motif 1 (CM1), which is widely found in γTuRC stimulators, including CDK5RAP2. Here, we show that a conserved segment within CM1 binds to the γTuNA and blocks its association with γTuRCs; therefore, we refer to this segment as the γTuNA inhibitor (γTuNA-In). Mutational disruption of the interaction between the γTuNA and the γTuNA-In results in a loss of autoinhibition, which consequently augments microtubule nucleation on centrosomes and the Golgi complex, the two major microtubule-organizing centers. This also causes centrosome repositioning, leads to defects in Golgi assembly and organization, and affects cell polarization. Remarkably, phosphorylation of the γTuNA-In, probably by Nek2, counteracts the autoinhibition by disrupting the γTuNA‒γTuNA-In interaction. Together, our data reveal an on-site mechanism for controlling γTuNA function.
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spelling pubmed-102028282023-11-22 Autoinhibitory mechanism controls binding of centrosomin motif 1 to γ-tubulin ring complex Yang, Shaozhong Au, Franco K.C. Li, Gefei Lin, Jianwei Li, Xiang David Qi, Robert Z. J Cell Biol Article The γ-tubulin ring complex (γTuRC) is the principal nucleator of cellular microtubules, and the microtubule-nucleating activity of the complex is stimulated by binding to the γTuRC-mediated nucleation activator (γTuNA) motif. The γTuNA is part of the centrosomin motif 1 (CM1), which is widely found in γTuRC stimulators, including CDK5RAP2. Here, we show that a conserved segment within CM1 binds to the γTuNA and blocks its association with γTuRCs; therefore, we refer to this segment as the γTuNA inhibitor (γTuNA-In). Mutational disruption of the interaction between the γTuNA and the γTuNA-In results in a loss of autoinhibition, which consequently augments microtubule nucleation on centrosomes and the Golgi complex, the two major microtubule-organizing centers. This also causes centrosome repositioning, leads to defects in Golgi assembly and organization, and affects cell polarization. Remarkably, phosphorylation of the γTuNA-In, probably by Nek2, counteracts the autoinhibition by disrupting the γTuNA‒γTuNA-In interaction. Together, our data reveal an on-site mechanism for controlling γTuNA function. Rockefeller University Press 2023-05-22 /pmc/articles/PMC10202828/ /pubmed/37213089 http://dx.doi.org/10.1083/jcb.202007101 Text en © 2023 Yang et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Yang, Shaozhong
Au, Franco K.C.
Li, Gefei
Lin, Jianwei
Li, Xiang David
Qi, Robert Z.
Autoinhibitory mechanism controls binding of centrosomin motif 1 to γ-tubulin ring complex
title Autoinhibitory mechanism controls binding of centrosomin motif 1 to γ-tubulin ring complex
title_full Autoinhibitory mechanism controls binding of centrosomin motif 1 to γ-tubulin ring complex
title_fullStr Autoinhibitory mechanism controls binding of centrosomin motif 1 to γ-tubulin ring complex
title_full_unstemmed Autoinhibitory mechanism controls binding of centrosomin motif 1 to γ-tubulin ring complex
title_short Autoinhibitory mechanism controls binding of centrosomin motif 1 to γ-tubulin ring complex
title_sort autoinhibitory mechanism controls binding of centrosomin motif 1 to γ-tubulin ring complex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202828/
https://www.ncbi.nlm.nih.gov/pubmed/37213089
http://dx.doi.org/10.1083/jcb.202007101
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