TPX2 is an elongated molecule containing multiple α-helical repeats. It stabilizes microtubules (MTs), promotes MT nucleation, and is essential for spindle assembly. However, the molecular basis of how TPX2 performs these functions remains elusive. Here, we systematically characterized the MT-binding activities of all TPX2 modules individually and in combinations and investigated their respective contributions both in vitro and in cells. We show that TPX2 contains α-helical repeats with opposite preferences for “extended” and “compacted” tubulin dimer spacing, and their distinct combinations produce divergent outcomes, making TPX2 activity highly robust yet tunable. Importantly, a repeat group at the C terminus, R8-9, is the key determinant of the TPX2 function. It stabilizes MTs by promoting rescues in vitro and is critical in spindle assembly. We propose a model where TPX2 activities are spatially regulated via its diverse MT-binding repeats to accommodate its varied functions in distinct locations within the spindle. Furthermore, we reveal a synergy between TPX2 and HURP in stabilizing spindle MTs.
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January 16 2025
Diverse microtubule-binding repeats regulate TPX2 activities at distinct locations within the spindle
Zhuobi Liang
,
Zhuobi Liang
*
(Conceptualization, Investigation, Methodology, Visualization, Writing - original draft)
1State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology,
School and Hospital of Stomatology, Medical Research Institute, Wuhan University
, Wuhan, China
2
Frontier Science Center for Immunology and Metabolism, Wuhan University
, Wuhan, China
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Junjie Huang
,
Junjie Huang
*
(Conceptualization, Investigation, Methodology, Visualization, Writing - original draft)
1State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology,
School and Hospital of Stomatology, Medical Research Institute, Wuhan University
, Wuhan, China
2
Frontier Science Center for Immunology and Metabolism, Wuhan University
, Wuhan, China
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Yong Wang
,
Yong Wang
*
(Investigation, Methodology, Visualization, Writing - original draft)
1State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology,
School and Hospital of Stomatology, Medical Research Institute, Wuhan University
, Wuhan, China
2
Frontier Science Center for Immunology and Metabolism, Wuhan University
, Wuhan, China
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Shasha Hua
,
(Conceptualization, Methodology, Visualization, Writing - original draft, Writing - review & editing)
1State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology,
School and Hospital of Stomatology, Medical Research Institute, Wuhan University
, Wuhan, China
2
Frontier Science Center for Immunology and Metabolism, Wuhan University
, Wuhan, China
Shasha Hua: [email protected]
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Kai Jiang
(Conceptualization, Funding acquisition, Methodology, Supervision, Visualization, Writing - original draft, Writing - review & editing)
1State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology,
School and Hospital of Stomatology, Medical Research Institute, Wuhan University
, Wuhan, China
2
Frontier Science Center for Immunology and Metabolism, Wuhan University
, Wuhan, China
Correspondence to Kai Jiang: [email protected]
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Zhuobi Liang
Conceptualization, Investigation, Methodology, Visualization, Writing - original draft
*
1State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology,
School and Hospital of Stomatology, Medical Research Institute, Wuhan University
, Wuhan, China
2
Frontier Science Center for Immunology and Metabolism, Wuhan University
, Wuhan, China
Junjie Huang
Conceptualization, Investigation, Methodology, Visualization, Writing - original draft
*
1State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology,
School and Hospital of Stomatology, Medical Research Institute, Wuhan University
, Wuhan, China
2
Frontier Science Center for Immunology and Metabolism, Wuhan University
, Wuhan, China
Yong Wang
Investigation, Methodology, Visualization, Writing - original draft
*
1State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology,
School and Hospital of Stomatology, Medical Research Institute, Wuhan University
, Wuhan, China
2
Frontier Science Center for Immunology and Metabolism, Wuhan University
, Wuhan, China
Shasha Hua
Conceptualization, Methodology, Visualization, Writing - original draft, Writing - review & editing
1State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology,
School and Hospital of Stomatology, Medical Research Institute, Wuhan University
, Wuhan, China
2
Frontier Science Center for Immunology and Metabolism, Wuhan University
, Wuhan, China
Kai Jiang
Conceptualization, Funding acquisition, Methodology, Supervision, Visualization, Writing - original draft, Writing - review & editing
1State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology,
School and Hospital of Stomatology, Medical Research Institute, Wuhan University
, Wuhan, China
2
Frontier Science Center for Immunology and Metabolism, Wuhan University
, Wuhan, China
Correspondence to Kai Jiang: [email protected]
Shasha Hua: [email protected]
Disclosures: The authors declare no competing interests exist.
*
Z. Liang, J. Huang, and Y. Wang contributed equally to this paper.
Received:
April 05 2024
Revision Received:
November 12 2024
Accepted:
December 20 2024
Online ISSN: 1540-8140
Print ISSN: 0021-9525
Funding
Funder(s):
National Natural Science Foundation of China
- Award Id(s): 32370735,32070705
Funder(s):
Fundamental Research Funds for the Central Universities
- Award Id(s): 2042022dx0003,2042023kf0212
© 2025 Liang et al.
2025
Liang et al.
This article is distributed under the terms as described at https://rupress.org/pages/terms102024/.
J Cell Biol (2025) 224 (3): e202404025.
Article history
Received:
April 05 2024
Revision Received:
November 12 2024
Accepted:
December 20 2024
Citation
Zhuobi Liang, Junjie Huang, Yong Wang, Shasha Hua, Kai Jiang; Diverse microtubule-binding repeats regulate TPX2 activities at distinct locations within the spindle. J Cell Biol 3 March 2025; 224 (3): e202404025. doi: https://doi.org/10.1083/jcb.202404025
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