PLK4 drives centriole amplification and apical surface area expansion in multiciliated cells
- Johns Hopkins University School of Medicine, United States
Abstract
Multiciliated cells (MCCs) are terminally differentiated epithelia that assemble multiple motile cilia used to promote fluid flow. To template these cilia, MCCs dramatically expand their centriole content during a process known as centriole amplification. In cycling cells, the master regulator of centriole assembly Polo-like kinase 4 (PLK4) is essential for centriole duplication; however recent work has questioned the role of PLK4 in centriole assembly in MCCs. To address this discrepancy, we created genetically engineered mouse models and demonstrated that both PLK4 protein and kinase activity are critical for centriole amplification in MCCs. Tracheal epithelial cells that fail centriole amplification accumulate large assemblies of centriole proteins and do not undergo apical surface area expansion. These results show that the initial stages of centriole assembly are conserved between cycling cells and MCCs and suggest that centriole amplification and surface area expansion are coordinated events.
Data availability
All data generated or analysed during this study are included in the Source Data file.
Article and author information
Author details
Andrew Jon Holland
Funding
National Institute of General Medical Sciences (R01GM114119)
- Andrew Jon Holland
National Institute of General Medical Sciences (R01GM133897)
- Andrew Jon Holland
National Cancer Institute (R01CA266199)
- Andrew Jon Holland
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jens Lüders, Institute for Research in Biomedicine, Spain
Ethics
Animal experimentation: Mice were housed and cared for in an AAALAC-accredited facility. All animal experiments were approved by the Johns Hopkins University Institute Animal Care and Use Committee (MO21M300). All studies employed a mixture of male and female mice and no differences between sexes were observed. Euthanasia was performed using isoflurane followed by cervical dislocation and every effort was made to minimize animal suffering.
Version history
- Received: May 31, 2022
- Preprint posted: June 7, 2022 (view preprint)
- Accepted: August 12, 2022
- Accepted Manuscript published: August 15, 2022 (version 1)
- Version of Record published: September 23, 2022 (version 2)
Copyright
© 2022, LoMastro et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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PLK4 drives centriole amplification and apical surface area expansion in multiciliated cells
eLife 11:e80643.
https://doi.org/10.7554/eLife.80643
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