Centriolar satellites expedite mother centriole remodeling to promote ciliogenesis
- University of Edinburgh, United Kingdom
- University of California, San Francisco, United States
- Lunenfeld-Tanenbaum Research Institute, Canada
- University of Valencia, Spain
Abstract
Centrosomes are orbited by centriolar satellites, dynamic multiprotein assemblies nucleated by Pericentriolar Material 1 (PCM1). To study the requirement for centriolar satellites, we generated mice lacking PCM1, a crucial component of satellites. Pcm1-/- mice display partially penetrant perinatal lethality with survivors exhibiting hydrocephalus, oligospermia and cerebellar hypoplasia, and variably expressive phenotypes such as hydronephrosis. As many of these phenotypes have been observed in human ciliopathies and satellites are implicated in cilia biology, we investigated whether cilia were affected. PCM1 was dispensable for ciliogenesis in many cell types, whereas Pcm1-/- multiciliated ependymal cells and human PCM1-/- retinal pigmented epithelial 1 (RPE1) cells showed reduced ciliogenesis. PCM1-/- RPE1 cells displayed reduced docking of the mother centriole to the ciliary vesicle and removal of CP110 and CEP97 from the distal mother centriole, indicating compromised early ciliogenesis. Similarly, Pcm1-/- ependymal cells exhibited reduced removal of CP110 from basal bodies in vivo. We propose that PCM1 and centriolar satellites facilitate efficient trafficking of proteins to and from centrioles, including the departure of CP110 and CEP97 to initiate ciliogenesis, and that the threshold to trigger ciliogenesis differs between cell types.
Data availability
Proteomics data files are be uploaded ProteomeXchange (Identifier: PXD031920), with the accession number is available with the paper.All analysis tools have been made available on GitHub (https://github.com/IGC-Advanced-Imaging-Resource/Hall2022_Paper), as described in Materials and Methods.
Article and author information
Author details
Vicente Herranz-Pérez
Laurence Pelletier
Funding
Medical Research Council (MR_UU_1201018/26)
- Emma A Hall
- Dhivya Kumar
- Patricia L Yeyati
- Lorraine Rose
- Lisa McKie
- Daniel O Dodd
- Peter A Tennant
- Roly Megaw
- Laura C Murphy
- Marisa F Ferreira
- Graeme Grimes
- Lucy Williams
- Tooba Quidwai
- Pleasantine Mill
Sandler Foundation
- Dhivya Kumar
Krembil Foundation
- Suzanna L Prosser
- Laurence Pelletier
European Commission (866355)
- Emma A Hall
- Daniel O Dodd
- Pleasantine Mill
Canadian Institutes of Health Research (167279)
- Suzanna L Prosser
- Laurence Pelletier
European Commission (702601)
- Suzanna L Prosser
National Institutes of Health (R01GM095941)
- Dhivya Kumar
- Vicente Herranz-Pérez
- Jose Manuel García-Verdugo
- Jeremy F Reiter
National Institutes of Health (R01AR054396)
- Dhivya Kumar
- Vicente Herranz-Pérez
- Jose Manuel García-Verdugo
- Jeremy F Reiter
National Institutes of Health (RO1HD089918)
- Dhivya Kumar
- Vicente Herranz-Pérez
- Jose Manuel García-Verdugo
- Jeremy F Reiter
National Institutes of Health (5K99GM140175)
- Dhivya Kumar
Jane Coffin Childs Memorial Fund for Medical Research
- Dhivya Kumar
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animals were maintained in SPF environment and studies carried out in accordance with the guidance issued by the Medical Research Council in "Responsibility in the Use of Animals in Medical Research" (July 1993) and licensed by the Home Office under the Animals (Scientific Procedures) Act 1986 under project license number P18921CDE in facilities at the University of Edinburgh (PEL 60/6025).
Copyright
© 2023, Hall 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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Centriolar satellites expedite mother centriole remodeling to promote ciliogenesis
eLife 12:e79299.
https://doi.org/10.7554/eLife.79299
Further reading
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Existence of cilia in the last eukaryotic common ancestor raises a fundamental question in biology: how the transcriptional regulation of ciliogenesis has evolved? One conceptual answer to this question is by an ancient transcription factor regulating ciliary gene expression in both uni- and multicellular organisms, but examples of such transcription factors in eukaryotes are lacking. Previously, we showed that an ancient transcription factor X chromosome-associated protein 5 (Xap5) is required for flagellar assembly in Chlamydomonas. Here, we show that Xap5 and Xap5-like (Xap5l) are two conserved pairs of antagonistic transcription regulators that control ciliary transcriptional programs during spermatogenesis. Male mice lacking either Xap5 or Xap5l display infertility, as a result of meiotic prophase arrest and sperm flagella malformation, respectively. Mechanistically, Xap5 positively regulates the ciliary gene expression by activating the key regulators including Foxj1 and Rfx families during the early stage of spermatogenesis. In contrast, Xap5l negatively regulates the expression of ciliary genes via repressing these ciliary transcription factors during the spermiogenesis stage. Our results provide new insights into the mechanisms by which temporal and spatial transcription regulators are coordinated to control ciliary transcriptional programs during spermatogenesis.
