Cetrosomes are the main microtubule organising centers (MTOC) of animal cells and thus are critical in regulating cell-cycle progression. Centrosomes nucleate microtubules during mitosis, allowing for chromosomal segregation. Each centrosome contains 2 centrioles arranged perpendicularly and surrounded by pericentriolar material (PCM).
For an intense literature review of centrosomes one might check the cited studies (28575670, 32860741, 26388440, 26373263, 33597927, 34308971)
Formation, Composition & dynamics (Assembly and disassembly)
Relation to human diseases
Proteome
Formation, Composition & dynamics of (Assembly and disassembly)
Each centrosome is made up of two barrel-shaped centrioles floating in a pericentriolar material matrix of proteins (PCM). In many animal cells, the centrosome serves as a primary microtubule organizing center (MTOC). The PCM, which works as a scaffold to recruit MT regulators and nucleators, such as -tubulin ring complexes (-TuRCs), determines the centrosome's MTOC activity. Mitotic kinases, such as Polo/polo-like kinase 1 (PLK1) and aurora kinase A, phosphorylate core PCM components, such as spindle-defective protein 2 (SPD-2)/CEP192, spindle-defective protein 5 (SPD-5), centrosomin (Cnn)/CDK5RAP2 (CEP215), and pericentrin (PCNT). These events cause the co-assembly of more PCM proteins and - TuRCs, resulting in two mitotic centrosomes with increased MTOC activity, which aid bipolar spindle assembly and subsequent chromosomal segregation (26373263). Emerging evidence suggests LLPS as the underlying mechanism for centrosome assembly (28575670 ,34308971, 32699013)
25047613 summarized key proteins important for PCM assembly.
Relation to human diseases
Since its discovery, the centrosome is increasingly being recognized as a most impactful organelle for it's role not only as primary microtubule organizing center but also as a major communication center for signal transduction pathways and as a center for proteolytic activities. It's significance for cell cycle regulation has been well studied and centrosome dysfunctions are implicated in numerous diseases and disorders (30062583, 18437411).
The link between alteration in the structure or the number of centrioles and human diseases like cancer (29363672, 26175433, 21680046) and brain (21407209, 21680046) and genetic disorders (15738963) is described.
29363672 summarized proteins involved in centriole number control, their functions and links to disease. 15738963 summarized the list of centrosomal proteins associated with human genetic disorders.
Targeting centrosomes as therapy for diseases like cancer is been addressed in the literature. For example, Polo-like kinases, cyclin-dependent kinases, Aurora kinases, and others are among the overexpressed centrosome-phosphorylating kinases in cancer cells. The inhibition of these overexpressed kinases is a key target in the fight against cancer cell proliferation (check 30062583 for detailed review).
Proteome
31076588 used cryo-Electron Tomography, proteomics and immunolabeling to study centrosomes isolated from the young lamb thymus. The MS proteomic data have been deposited with the ProteomeXchange (accession code PXD003928).
27539480 used targeted proteomics and EGFP-tagging of centrosomal proteins at endogenous loci, to measure protein abundance in cultured human cells and purified centrosomes. The raw mass spectrometric data used in this study and the Mascot analysis files are available via ProteomeXchange (accession code PXD003927 ).
8971254 provided a human centrosomal proteins database (Centrosome:db ) which compiled a set of 383 likely human centrosomal genes and recorded the associated supporting evidences. Centrosome:db is publicly available at http://centrosome.dacya.ucm.es.
14654843 performed a mass-spectrometry-based proteomic analysis of human centrosomes in the interphase of the cell cycle by quantitatively profiling hundreds of proteins across several centrifugation fractions. This study identified and validated 23 novel components and identified 41 likely candidates.
References
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