Lu, H., Goh, K.J., Tan, E.K. et al. (10 more authors) (2025) Nuclear-cytoplasmic translocation of MCIDAS couples transcription with massive de novo centriole biogenesis in multiciliated cells. Cell Reports, 44 (10). 116321. ISSN: 2211-1247
Abstract
Multiciliated cells (MCCs) bear numerous motile cilia that drive fluid flow, but how numerous centrioles for multiciliation are generated has remained unresolved. Here, we report that the “master” MCC transcriptional regulator, MCIDAS, moonlights in the cytoplasm to organize massive centriole biogenesis. Like MCIDAS, its co-transcriptional factors, E2F4 and E2F5, also undergo cytoplasmic accumulation, colocalizing with MCIDAS and forming procentrioles. MCIDAS loss inhibited E2F4/5 cytoplasmic accumulation and blocked centriole assembly. Furthermore, we show that the cytoplasmic accumulation of MCIDAS is mediated by CRM1-dependant nuclear export, and its inhibition specifically compromised centriole biogenesis. By contrast, on loss of parental centrioles and deuterosomes, which does not impair centriole formation, E2F4 cytoplasmic localization remained unaffected, establishing that the MCIDAS-E2F4/5 cytoplasmic complex represents the de novo centriole biogenesis pathway. We have also assembled a comprehensive list of MCIDAS targets, a resource which will enable further exposition of MCC biology and pathological mechanisms of motile ciliopathies.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | multiciliated cells; centrioles; de novo centriole biogenesis; MCIDAS; E2F4; E2F5; human embryonic stem cells; mouse tracheal epithelial cells; ependymal cells; primary ciliary dyskinesia |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 23 Sep 2025 15:27 |
Last Modified: | 24 Sep 2025 00:42 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/j.celrep.2025.116321 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:232055 |
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Filename: Bingle Cell Reports 10.1016:j.celrep.2025.116321 Sep2025.pdf
Licence: CC-BY 4.0