Centriolar satellites expedite mother centriole remodeling to promote ciliogenesis.

Autor:	Hall EA; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom., Kumar D; Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, United States., Prosser SL; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada., Yeyati PL; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom., Herranz-Pérez V; Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, Valencia, Spain.; Predepartamental Unit of Medicine, Jaume I University, Castelló de la Plana, Spain., García-Verdugo JM; Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, Valencia, Spain., Rose L; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom., McKie L; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom., Dodd DO; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom., Tennant PA; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom., Megaw R; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom., Murphy LC; Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom., Ferreira MF; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom., Grimes G; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom., Williams L; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom., Quidwai T; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom., Pelletier L; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.; Department of Molecular Genetics, University of Toronto, University of Toronto, Canada., Reiter JF; Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, United States.; Chan Zuckerberg Biohub, San Francisco, United States., Mill P; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2023 Feb 15; Vol. 12. Date of Electronic Publication: 2023 Feb 15.
DOI:	10.7554/eLife.79299
Abstrakt:	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. Competing Interests: EH, DK, SP, PY, VH, JG, LR, LM, DD, PT, RM, LM, MF, GG, LW, TQ, LP, PM No competing interests declared, JR Reviewing editor, eLife (© 2023, Hall, Kumar et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu