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Differential requirement for centriolar satellites in cilium formation among different vertebrate cells

Ezgi Odabasi, Signe K. Ohlsen, Seref Gul, Ibrahim H. Kavakli, Jens S. Andersen, Elif N. Firat-Karalar
doi: https://doi.org/10.1101/478974
Ezgi Odabasi
1Department of Molecular Biology and Genetics, Koç University, Istanbul, Turkey 34450
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Signe K. Ohlsen
2Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark
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Seref Gul
1Department of Molecular Biology and Genetics, Koç University, Istanbul, Turkey 34450
3Department of Chemical and Biological Engineering, Koç University, Istanbul, Turkey 34450
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Ibrahim H. Kavakli
1Department of Molecular Biology and Genetics, Koç University, Istanbul, Turkey 34450
3Department of Chemical and Biological Engineering, Koç University, Istanbul, Turkey 34450
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Jens S. Andersen
2Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark
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Elif N. Firat-Karalar
1Department of Molecular Biology and Genetics, Koç University, Istanbul, Turkey 34450
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Abstract

Centriolar satellites are ubiquitous in vertebrate cells. They have recently emerged as key regulators of centrosome/cilium biogenesis, and their mutations are linked to ciliopathies. However, their precise functions and mechanisms of action, which potentially differ between cell types, remain poorly understood. Here, we generated retinal pigmental and kidney epithelial cells lacking satellites by genetically ablating PCM1 to investigate their functions. While satellites were essential for cilium assembly in retinal epithelial cells, kidney epithelial cells lacking satellites still formed full-length cilia but at significantly lower levels, with reduced centrosomal levels of key ciliogenesis factors. Using these cells, we identified the first satellite-specific functions at cilia, specifically in regulating ciliary content, Hedgehog signalling, and epithelial cell organization. However, other satellite-linked functions, namely proliferation, cell cycle progression and centriole duplication, were unaffected in these cells. Quantitative transcriptomic and proteomic profiling revealed that loss of satellites scarcely affects transcription, but significantly alters the proteome, particularly actin cytoskeleton pathways and neuronal functions. Together, our findings identify cell type-specific roles for satellites and provide insight into the phenotypic heterogeneity of ciliopathies.

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Posted November 26, 2018.
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Differential requirement for centriolar satellites in cilium formation among different vertebrate cells
Ezgi Odabasi, Signe K. Ohlsen, Seref Gul, Ibrahim H. Kavakli, Jens S. Andersen, Elif N. Firat-Karalar
bioRxiv 478974; doi: https://doi.org/10.1101/478974
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Differential requirement for centriolar satellites in cilium formation among different vertebrate cells
Ezgi Odabasi, Signe K. Ohlsen, Seref Gul, Ibrahim H. Kavakli, Jens S. Andersen, Elif N. Firat-Karalar
bioRxiv 478974; doi: https://doi.org/10.1101/478974

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