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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Mechanical forces play a critical role in tendon development and function, influencing cell behavior through mechanotransduction signaling pathways and subsequent extracellular matrix (ECM) remodeling. Here we investigate the molecular mechanisms by which tenocytes in developing zebrafish embryos respond to muscle contraction forces during the onset of swimming and cranial muscle activity. Using genome-wide bulk RNA sequencing of FAC-sorted tenocytes we identify novel tenocyte markers and genes involved in tendon mechanotransduction. Embryonic tendons show dramatic changes in expression of matrix remodeling associated 5b (mxra5b), matrilin1 (matn1), and the transcription factor kruppel-like factor 2a (klf2a), as muscles start to contract. Using embryos paralyzed either by loss of muscle contractility or neuromuscular stimulation we confirm that muscle contractile forces influence the spatial and temporal expression patterns of all three genes. Quantification of these gene expression changes across tenocytes at multiple tendon entheses and myotendinous junctions reveals that their responses depend on force intensity, duration and tissue stiffness. These force-dependent feedback mechanisms in tendons, particularly in the ECM, have important implications for improved treatments of tendon injuries and atrophy.
