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

ABSTRACT: Centriolar satellites are an array of membrane-less granules that localize and move around the vertebrate centrosome/cilium complex. They have recently emerged as key regulators of the biogenesis and function of the centrosome/cilium-complex and their mutations are linked to ciliopathies. Although centriolar satellites are ubiquitous structures of the vertebrate cells, their precise function and molecular mechanism of action in different cell types remain poorly understood. Here, we generated kidney and retinal epithelial cells that lack centriolar satellites by genetically ablating their scaffolding protein PCM1 and investigated the cellular and molecular consequences of satellite loss in cells. We showed that centriolar satellites are required for cilium assembly, regulation of ciliary content, timely response to Hedgehog signals and three- dimensional epithelial cell organization, but not for cell proliferation, cell cycle progression and centriole duplication. Importantly, the requirement for centriolar satellites in cilium assembly varied between retinal and kidney epithelial cells and we identified the differences in the efficiency of targeting key ciliogenesis factors to the centrosome including Mib1 and Talpid3 as the likely molecular basis for this phenotypic variability. Quantitative global transcriptomic and proteomic profiling of satellite-less cells showed that loss of centriolar satellites does not lead to a major transcriptional response, but leads to a significant rearrangement of the global proteome. Together, our findings identify important roles for centriolar satellites in key cilium-related cellular processes through regulating the proteostasis and centrosomal/ciliary targeting of proteins and provide insight into the disease mechanisms of ciliopathies.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE123017 | GEO | 2018/11/28

REPOSITORIES: GEO