Delta tubulin (TUBD1) is a noncanonical tubulin protein that has been linked to complex microtubule structures in somatic cell lines and unicellular species. Its role in mammals remains enigmatic; however, TUBD1 is enriched within mammalian male germ cells. Herein, we have defined new roles for TUBD1 during male germ cell development in vivo using a conditional knockout mouse model and shown that spermatogenesis in the absence of TUBD1 causes sterility. We show TUBD1 stabilizes kinetochores during male mouse meiosis, enabling meiotic progression, and that it is required for appropriate spindle polarity and cytokinesis. Subsequently, in haploid cells, TUBD1 works in partnership with the microtubule-severing enzymes KATNAL2 and KATNB1 to regulate manchette remodeling and shape the sperm head. Collectively, these findings reveal TUBD1 plays a key role in the formation and function of highly specialized microtubule structures in mammalian spermatogenesis. Advanced knowledge of TUBD1 may generate new insights into underlying causes of diseases associated with infertility or development.
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June 30 2025
Delta tubulin stabilizes male meiotic kinetochores and aids microtubule remodeling and fertility
G. Gemma Stathatos
,
G. Gemma Stathatos
(Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Visualization, Writing - original draft, Writing - review & editing)
1
School of BioSciences and Bio21 Molecular Sciences and Biotechnology Institute, Faculty of Science, The University of Melbourne
, Parkville, Australia
2
Australian Regenerative Medicine Institute, Monash University
, Clayton, Australia
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D. Jo Merriner
,
D. Jo Merriner
(Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Validation, Visualization, Writing - review & editing)
1
School of BioSciences and Bio21 Molecular Sciences and Biotechnology Institute, Faculty of Science, The University of Melbourne
, Parkville, Australia
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Anne E. O’Connor
,
Anne E. O’Connor
(Investigation)
1
School of BioSciences and Bio21 Molecular Sciences and Biotechnology Institute, Faculty of Science, The University of Melbourne
, Parkville, Australia
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Jennifer Zenker
,
Jennifer Zenker
(Methodology, Supervision, Visualization, Writing - original draft, Writing - review & editing)
2
Australian Regenerative Medicine Institute, Monash University
, Clayton, Australia
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Jessica E.M. Dunleavy
,
(Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Supervision, Writing - original draft, Writing - review & editing)
1
School of BioSciences and Bio21 Molecular Sciences and Biotechnology Institute, Faculty of Science, The University of Melbourne
, Parkville, Australia
Jessica E.M. Dunleavy: [email protected]
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Moira K. O’Bryan
(Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Visualization, Writing - original draft, Writing - review & editing)
1
School of BioSciences and Bio21 Molecular Sciences and Biotechnology Institute, Faculty of Science, The University of Melbourne
, Parkville, Australia
Correspondence to Moira K. O’Bryan: [email protected]
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G. Gemma Stathatos
Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Visualization, Writing - original draft, Writing - review & editing
1
School of BioSciences and Bio21 Molecular Sciences and Biotechnology Institute, Faculty of Science, The University of Melbourne
, Parkville, Australia
2
Australian Regenerative Medicine Institute, Monash University
, Clayton, Australia
D. Jo Merriner
Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Validation, Visualization, Writing - review & editing
1
School of BioSciences and Bio21 Molecular Sciences and Biotechnology Institute, Faculty of Science, The University of Melbourne
, Parkville, Australia
Anne E. O’Connor
Investigation
1
School of BioSciences and Bio21 Molecular Sciences and Biotechnology Institute, Faculty of Science, The University of Melbourne
, Parkville, Australia
Jennifer Zenker
Methodology, Supervision, Visualization, Writing - original draft, Writing - review & editing
2
Australian Regenerative Medicine Institute, Monash University
, Clayton, Australia
Jessica E.M. Dunleavy
Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Supervision, Writing - original draft, Writing - review & editing
1
School of BioSciences and Bio21 Molecular Sciences and Biotechnology Institute, Faculty of Science, The University of Melbourne
, Parkville, Australia
Moira K. O’Bryan
Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Visualization, Writing - original draft, Writing - review & editing
1
School of BioSciences and Bio21 Molecular Sciences and Biotechnology Institute, Faculty of Science, The University of Melbourne
, Parkville, Australia
Correspondence to Moira K. O’Bryan: [email protected]
Jessica E.M. Dunleavy: [email protected]
Disclosures: The authors declare no competing interests exist.
Received:
December 06 2024
Revision Received:
May 01 2025
Accepted:
June 13 2025
Online ISSN: 1540-8140
Print ISSN: 0021-9525
Funding
Funder(s):
Australian Government Research Training Program Scholarship
Funder(s):
National Health and Medical Research Council
- Award Id(s): APP1180929,APP2002507,APP2009409
Funder(s):
Australian Research Council
- Award Id(s): DP160100647
Funder(s):
Sylvia and Charles Viertel Fellowship
Funder(s):
Canadian Institute for Advanced Research
Funder(s):
Australian Regenerative Medicine Institute
© 2025 Stathatos et al.
2025
Stathatos et al.
This article is distributed under the terms as described at https://rupress.org/pages/terms102024/.
J Cell Biol (2025) 224 (9): e202412056.
Article history
Received:
December 06 2024
Revision Received:
May 01 2025
Accepted:
June 13 2025
Citation
G. Gemma Stathatos, D. Jo Merriner, Anne E. O’Connor, Jennifer Zenker, Jessica E.M. Dunleavy, Moira K. O’Bryan; Delta tubulin stabilizes male meiotic kinetochores and aids microtubule remodeling and fertility. J Cell Biol 1 September 2025; 224 (9): e202412056. doi: https://doi.org/10.1083/jcb.202412056
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