Centriolar satellites expedite mother centriole remodeling to promote ciliogenesis

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.Editor's evaluation This manuscript will be of interest to centrosome and cilia cell biologists and evaluates the in vivo and in vitro role of PCM1, and by extension, centriole satellites in ciliogenesis. The major strength of this study is the detailed characterization of Pcm1-/- mutant mice, which reveals a role for PCM1 in the biogenesis of specific types of cilia, such as motile cilia on ependymal cells, by a mechanism involving CP110 and CEP97. The claims are generally well supported by the data.

Automated summary

By generating mice lacking PCM1, this study reveals the important role of PCM1 and centriolar satellites in ciliogenesis, specifically in motile cilia on ependymal cells. The findings demonstrate that PCM1 is involved in efficient protein trafficking to and from centrioles, including the removal of CP110 and CEP97 to initiate ciliogenesis, and the threshold for ciliogenesis differs between cell types.