A delta-tubulin/epsilon-tubulin/Ted protein complex is required for centriole architecture
Centrioles have a unique, conserved architecture formed by three linked, ‘triplet’, microtubules arranged in ninefold symmetry. The mechanisms by which these triplet microtubules are formed remain unclear but likely involve the noncanonical tubulins delta-tubulin and epsilon-tubulin. Previously, we...
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eLife Sciences Publications Ltd
2025-03-01
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| Online Access: | https://elifesciences.org/articles/98704 |
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| author | Rachel Pudlowski Lingyi Xu Ljiljana Milenkovic Chandan Kumar Katherine Hemsworth Zayd Aqrabawi Tim Stearns Jennifer T Wang |
| author_facet | Rachel Pudlowski Lingyi Xu Ljiljana Milenkovic Chandan Kumar Katherine Hemsworth Zayd Aqrabawi Tim Stearns Jennifer T Wang |
| author_sort | Rachel Pudlowski |
| collection | DOAJ |
| description | Centrioles have a unique, conserved architecture formed by three linked, ‘triplet’, microtubules arranged in ninefold symmetry. The mechanisms by which these triplet microtubules are formed remain unclear but likely involve the noncanonical tubulins delta-tubulin and epsilon-tubulin. Previously, we found that human cells lacking delta-tubulin or epsilon-tubulin form abnormal centrioles, characterized by an absence of triplet microtubules, lack of central core protein POC5, and a futile cycle of centriole formation and disintegration (Wang et al., 2017). Here, we show that human cells lacking either TEDC1 or TEDC2 have similar abnormalities. Using ultrastructure expansion microscopy, we observed that mutant centrioles elongate to the same length as control centrioles in G2 phase and fail to recruit central core scaffold proteins. Remarkably, mutant centrioles also have an expanded proximal region. During mitosis, these mutant centrioles further elongate before fragmenting and disintegrating. All four proteins physically interact and TEDC1 and TEDC2 can form a subcomplex in the absence of the tubulins, supporting an AlphaFold Multimer model of the tetramer. TEDC1 and TEDC2 localize to centrosomes and are mutually dependent on each other and on delta-tubulin and epsilon-tubulin for localization. Our results demonstrate that delta-tubulin, epsilon-tubulin, TEDC1, and TEDC2 function together to promote robust centriole architecture, laying the foundation for future studies on the mechanisms underlying the assembly of triplet microtubules and their interactions with centriole structure. |
| format | Article |
| id | doaj-art-9ef22289f18b4e5cacb89f3e00410b83 |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-03-01 |
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| series | eLife |
| spelling | doaj-art-9ef22289f18b4e5cacb89f3e00410b832025-08-20T02:48:12ZengeLife Sciences Publications LtdeLife2050-084X2025-03-011310.7554/eLife.98704A delta-tubulin/epsilon-tubulin/Ted protein complex is required for centriole architectureRachel Pudlowski0https://orcid.org/0009-0002-7767-1147Lingyi Xu1Ljiljana Milenkovic2Chandan Kumar3Katherine Hemsworth4Zayd Aqrabawi5Tim Stearns6https://orcid.org/0000-0002-0671-6582Jennifer T Wang7https://orcid.org/0000-0002-8506-5182Department of Biology, Washington University in St. Louis, St. Louis, United StatesDepartment of Biology, Washington University in St. Louis, St. Louis, United StatesDepartment of Biology, Stanford University, Stanford, United StatesDepartment of Biology, Washington University in St. Louis, St. Louis, United StatesDepartment of Biology, Washington University in St. Louis, St. Louis, United StatesDepartment of Biology, Washington University in St. Louis, St. Louis, United StatesDepartment of Biology, Stanford University, Stanford, United States; Rockefeller University, New York City, United StatesDepartment of Biology, Washington University in St. Louis, St. Louis, United StatesCentrioles have a unique, conserved architecture formed by three linked, ‘triplet’, microtubules arranged in ninefold symmetry. The mechanisms by which these triplet microtubules are formed remain unclear but likely involve the noncanonical tubulins delta-tubulin and epsilon-tubulin. Previously, we found that human cells lacking delta-tubulin or epsilon-tubulin form abnormal centrioles, characterized by an absence of triplet microtubules, lack of central core protein POC5, and a futile cycle of centriole formation and disintegration (Wang et al., 2017). Here, we show that human cells lacking either TEDC1 or TEDC2 have similar abnormalities. Using ultrastructure expansion microscopy, we observed that mutant centrioles elongate to the same length as control centrioles in G2 phase and fail to recruit central core scaffold proteins. Remarkably, mutant centrioles also have an expanded proximal region. During mitosis, these mutant centrioles further elongate before fragmenting and disintegrating. All four proteins physically interact and TEDC1 and TEDC2 can form a subcomplex in the absence of the tubulins, supporting an AlphaFold Multimer model of the tetramer. TEDC1 and TEDC2 localize to centrosomes and are mutually dependent on each other and on delta-tubulin and epsilon-tubulin for localization. Our results demonstrate that delta-tubulin, epsilon-tubulin, TEDC1, and TEDC2 function together to promote robust centriole architecture, laying the foundation for future studies on the mechanisms underlying the assembly of triplet microtubules and their interactions with centriole structure.https://elifesciences.org/articles/98704centrosomecentriolemicrotubulestriplet microtubulesciliamicrotubule organizing center |
| spellingShingle | Rachel Pudlowski Lingyi Xu Ljiljana Milenkovic Chandan Kumar Katherine Hemsworth Zayd Aqrabawi Tim Stearns Jennifer T Wang A delta-tubulin/epsilon-tubulin/Ted protein complex is required for centriole architecture eLife centrosome centriole microtubules triplet microtubules cilia microtubule organizing center |
| title | A delta-tubulin/epsilon-tubulin/Ted protein complex is required for centriole architecture |
| title_full | A delta-tubulin/epsilon-tubulin/Ted protein complex is required for centriole architecture |
| title_fullStr | A delta-tubulin/epsilon-tubulin/Ted protein complex is required for centriole architecture |
| title_full_unstemmed | A delta-tubulin/epsilon-tubulin/Ted protein complex is required for centriole architecture |
| title_short | A delta-tubulin/epsilon-tubulin/Ted protein complex is required for centriole architecture |
| title_sort | delta tubulin epsilon tubulin ted protein complex is required for centriole architecture |
| topic | centrosome centriole microtubules triplet microtubules cilia microtubule organizing center |
| url | https://elifesciences.org/articles/98704 |
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