Centriolar satellites expedite mother centriole remodeling to promote ciliogenesis.

Hall, E. A.; Kumar, D.; Prosser, S. L.; Yeyati, P. L.; Herranz-Pérez, V.; Garcia Verdugo, J. M.; Rose, L.; McKie, L.; Dodd, D. O.; Tennant, P. A.; Megaw, R.; Murphy, L. C.; Ferreira, M.; Grimes, G.; Williams, L.; Pelletier, L.; Quidwai, T.; Reiter, J. F.; Mill, P.

doi:10.1101/2022.04.04.486992

bioRxiv · 10.1101/2022.04.04.486992

Centriolar satellites expedite mother centriole remodeling to promote ciliogenesis.

Hall, E. A.·Kumar, D.·Prosser, S. L.·Yeyati, P. L.·Herranz-Pérez, V.·Garcia Verdugo, J. M.·Rose, L.·McKie, L.·Dodd, D. O.·Tennant, P. A.·Megaw, R.·Murphy, L. C.·Ferreira, M.·Grimes, G.·Williams, L.·Pelletier, L.·Quidwai, T.·Reiter, J. F.·Mill, P.

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Abstract

Centrosomes are orbited by centriolar satellites, dynamic multiprotein assemblies nucleated by PCM1. To study the requirement for centriolar satellites, we generated mice lacking PCM1. Pcm1-/- mice display partially penetrant perinatal lethality with survivors exhibiting hydrocephalus, oligospermia and cerebellar hypoplasia, as well as variable expressivity of other ciliopathy features including cystic kidneys. Pcm1-/- multiciliated ependymal cells and 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 compromized early ciliogenesis. We show these molecular cascades are maintained in vivo, and we suggest that the cellular threshold to trigger ciliogenesis varies between cell types. We propose that PCM1 and centriolar satellites facilitate efficient trafficking of proteins to and from centrioles, inducing the departure of CP110 and CEP97 to initiate ciliogenesis.

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Hall, E. A., Kumar, D., Prosser, S. L., Yeyati, P. L., Herranz-Pérez, V., Garcia Verdugo, J. M., Rose, L., McKie, L., Dodd, D. O., Tennant, P. A., Megaw, R., Murphy, L. C., Ferreira, M., Grimes, G., Williams, L., Pelletier, L., Quidwai, T., Reiter, J. F., Mill, P.. 2022-04-04. Centriolar satellites expedite mother centriole remodeling to promote ciliogenesis.. https://doi.org/10.1101/2022.04.04.486992

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