Centriolar satellites are acentriolar assemblies of centrosomal proteins.

Centrioles are core structural elements of both centrosomes and cilia. Although cytoplasmic granules called centriolar satellites have been observed around these structures, lack of a comprehensive inventory of satellite proteins impedes our understanding of their ancestry. To address this, we performed mass spectrometry (MS)-based proteome profiling of centriolar satellites obtained by affinity purification of their key constituent, PCM1, from sucrose gradient fractions. We defined an interactome consisting of 223 proteins, which showed striking enrichment in centrosome components. The proteome also contained new structural and regulatory factors with roles in ciliogenesis. Quantitative MS on whole-cell and centriolar satellite proteomes of acentriolar cells was performed to reveal dependencies of satellite composition on intact centrosomes. Although most components remained associated with PCM1 in acentriolar cells, reduced cytoplasmic and satellite levels were observed for a subset of centrosomal proteins. These results demonstrate that centriolar satellites and centrosomes form independently but share a substantial fraction of their proteomes. Dynamic exchange of proteins between these organelles could facilitate their adaptation to changing cellular environments during development, stress response and tissue homeostasis.

Molecular landscape and functional characterization of centrosome amplification in ovarian cancer.

High-grade serous ovarian carcinoma (HGSOC) is characterised by poor outcome and extreme chromosome instability (CIN). Therapies targeting centrosome amplification (CA), a key mediator of chromosome missegregation, may have significant clinical utility in HGSOC. However, the prevalence of CA in HGSOC, its relationship to genomic biomarkers of CIN and its potential impact on therapeutic response have not been defined. Using high-throughput multi-regional microscopy on 287 clinical HGSOC tissues and 73 cell lines models, here we show that CA through centriole overduplication is a highly recurrent and heterogeneous feature of HGSOC and strongly associated with CIN and genome subclonality. Cell-based studies showed that high-prevalence CA is phenocopied in ovarian cancer cell lines, and that high CA is associated with increased multi-treatment resistance; most notably to paclitaxel, the commonest treatment used in HGSOC. CA in HGSOC may therefore present a potential driver of tumour evolution and a powerful biomarker for response to standard-of-care treatment.

Accessorizing the centrosome: new insights into centriolar appendages and satellites.

Centrosomes comprise two centrioles, the mother and daughter, embedded within a multi-layered proteinaceous matrix known as the pericentriolar material. In proliferating cells, centrosomes duplicate once per cell cycle and organise interphase and mitotic microtubule arrays, whereas in quiescent cells, the mother centriole templates primary cilium formation. Centrosomes have acquired various accessory structures to facilitate these disparate functions. In some eukaryotic lineages, mother centrioles can be distinguished from their daughter by the presence of appendages at their distal end, which anchor microtubule minus ends and tether Golgi-derived vesicles involved in ciliogenesis. Moreover, in vertebrate cells, centrosomes are surrounded by a system of cytoplasmic granules known as centriolar satellites. In this review, we will discuss these centriolar accessories and outline recent findings pertaining to their composition, assembly and regulation.