Centriolar satellites expedite mother centriole remodeling to promote ciliogenesis
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- Emma A Hall
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh
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- Dhivya Kumar
- Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California
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- Suzanna L Prosser
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System
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- Patricia L Yeyati
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh
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- Vicente Herranz-Pérez
- Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia
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- Jose Manuel García-Verdugo
- Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia
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- Lorraine Rose
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh
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- Lisa McKie
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh
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- Daniel O Dodd
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh
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- Peter A Tennant
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh
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- Roly Megaw
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh
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- Laura C Murphy
- Institute of Genetics and Cancer, University of Edinburgh
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- Marisa F Ferreira
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh
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- Graeme Grimes
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh
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- Lucy Williams
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh
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- Tooba Quidwai
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh
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- Laurence Pelletier
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System
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- Jeremy F Reiter
- Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California
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- Pleasantine Mill
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh
抄録
<jats:p>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. <jats:italic>Pcm1<jats:sup>−/−</jats:sup></jats:italic> 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 <jats:italic>Pcm1<jats:sup>−/−</jats:sup></jats:italic> multiciliated ependymal cells and human <jats:italic>PCM1<jats:sup>−/−</jats:sup></jats:italic> retinal pigmented epithelial 1 (RPE1) cells showed reduced ciliogenesis. <jats:italic>PCM1<jats:sup>−/−</jats:sup></jats:italic> 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, <jats:italic>Pcm1<jats:sup>−/−</jats:sup></jats:italic> 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.</jats:p>
収録刊行物
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- eLife
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eLife 12 2023-02-15
eLife Sciences Publications, Ltd