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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May 22 2023
Autoinhibitory mechanism controls binding of centrosomin motif 1 to γ-tubulin ring complex
Shaozhong Yang
,
Shaozhong Yang
(Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing)
1
Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology
, Hong Kong, China
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Franco K.C. Au
,
Franco K.C. Au
(Investigation, Writing - review & editing)
1
Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology
, Hong Kong, China
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Gefei Li
,
Gefei Li
(Data curation, Investigation, Writing - review & editing)
1
Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology
, Hong Kong, China
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Jianwei Lin
,
Jianwei Lin
(Formal analysis, Resources)
2Department of Chemistry,
The University of Hong Kong
, Hong Kong, China
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Xiang David Li
,
Xiang David Li
(Methodology, Project administration, Supervision)
2Department of Chemistry,
The University of Hong Kong
, Hong Kong, China
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Robert Z. Qi
(Conceptualization, Data curation, Funding acquisition, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing)
1
Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology
, Hong Kong, China
3
Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou)
, Guangzhou, China
Correspondence to Robert Z. Qi: qirz@ust.hk
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Shaozhong Yang
Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology
, Hong Kong, China
Franco K.C. Au
Investigation, Writing - review & editing
1
Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology
, Hong Kong, China
Gefei Li
Data curation, Investigation, Writing - review & editing
1
Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology
, Hong Kong, China
Jianwei Lin
Formal analysis, Resources
2Department of Chemistry,
The University of Hong Kong
, Hong Kong, China
Xiang David Li
Methodology, Project administration, Supervision
2Department of Chemistry,
The University of Hong Kong
, Hong Kong, China
Robert Z. Qi
Conceptualization, Data curation, Funding acquisition, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology
, Hong Kong, China
3
Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou)
, Guangzhou, China
Correspondence to Robert Z. Qi: qirz@ust.hk
Disclosures: The authors declare no competing interests exist.
S. Yang’s current affiliation is Department of Neurobiology, Affiliated Mental Health Center and Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
F.K.C. Au’s current affiliation is Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA.
Received:
July 16 2020
Revision Received:
January 03 2023
Accepted:
March 24 2023
Online ISSN: 1540-8140
Print ISSN: 0021-9525
Funding
Funder(s):
Research Grants Council, University Grants Committee
- Award Id(s): 16100820
Funder(s):
Theme-based Research Scheme
- Award Id(s): T13-605/18-W
Funder(s):
Innovation and Technology Commission - Hong Kong
- Award Id(s): ITCPD/17-9
Funder(s):
Shenzhen Science and Technology Innovation Program
- Award Id(s): SGDX20210823103200005
Funder(s):
Postdoctoral Fellowship Scheme
- Award Id(s): PDFS2021-6S03
© 2023 Yang et al.
2023
Yang et al.
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/).
J Cell Biol (2023) 222 (7): e202007101.
Article history
Received:
July 16 2020
Revision Received:
January 03 2023
Accepted:
March 24 2023
Citation
Shaozhong Yang, Franco K.C. Au, Gefei Li, Jianwei Lin, Xiang David Li, Robert Z. Qi; Autoinhibitory mechanism controls binding of centrosomin motif 1 to γ-tubulin ring complex. J Cell Biol 3 July 2023; 222 (7): e202007101. doi: https://doi.org/10.1083/jcb.202007101
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