Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation

被引:51
|
作者
Odabasi, Ezgi [1 ]
Gul, Seref [1 ,2 ]
Kavakli, Ibrahim H. [1 ,2 ]
Firat-Karalar, Elif N. [1 ]
机构
[1] Koc Univ, Dept Mol Biol & Genet, Istanbul, Turkey
[2] Koc Univ, Dept Chem & Biol Engn, Istanbul, Turkey
基金
欧洲研究理事会;
关键词
centriolar satellites; Hedgehog; PCM1; primary cilium; MICROTUBULE-ORGANIZING CENTERS; MOLECULAR CHARACTERIZATION; INTRAFLAGELLAR TRANSPORT; BBS PROTEINS; CENTROSOME; CILIUM; COMPONENTS; INTERACTS; PCM1; GENE;
D O I
10.15252/embr.201947723
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 remain poorly understood. Here, we generated a kidney epithelial cell line (IMCD3) lacking satellites by CRISPR/Cas9-mediated PCM1 deletion and investigated the cellular and molecular consequences of satellite loss. Cells lacking satellites still formed full-length cilia but at significantly lower numbers, with changes in the centrosomal and cellular levels of key ciliogenesis factors. Using these cells, we identified new ciliary functions of satellites such as regulation of ciliary content, Hedgehog signaling, and epithelial cell organization in three-dimensional cultures. However, other functions of satellites, namely proliferation, cell cycle progression, and centriole duplication, were unaffected in these cells. Quantitative transcriptomic and proteomic profiling revealed that loss of satellites affects transcription scarcely, but significantly alters the proteome. Importantly, the centrosome proteome mostly remains unaltered in the cells lacking satellites. Together, our findings identify centriolar satellites as regulators of efficient cilium assembly and function and provide insight into disease mechanisms of ciliopathies.
引用
收藏
页数:20
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