The centrosome cycle: Centriole biogenesis, duplication and inherent asymmetries
Erich A. Nigg,Tim Stearns +1 more
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TLDR
The spatial aspects of the centrosome duplication cycle, the mechanism of centriole assembly and the possible consequences of the inherent asymmetry of Centrosomes and centrosomes are discussed.Abstract:
Centrosomes are microtubule-organizing centres of animal cells. They influence the morphology of the microtubule cytoskeleton, function as the base for the primary cilium and serve as a nexus for important signalling pathways. At the core of a typical centrosome are two cylindrical microtubule-based structures termed centrioles, which recruit a matrix of associated pericentriolar material. Cells begin the cell cycle with exactly one centrosome, and the duplication of centrioles is constrained such that it occurs only once per cell cycle and at a specific site in the cell. As a result of this duplication mechanism, the two centrioles differ in age and maturity, and thus have different functions; for example, the older of the two centrioles can initiate the formation of a ciliary axoneme. We discuss spatial aspects of the centrosome duplication cycle, the mechanism of centriole assembly and the possible consequences of the inherent asymmetry of centrioles and centrosomes.read more
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Parkinson disease-associated mutations in LRRK2 cause centrosomal defects via Rab8a phosphorylation
Jesús Madero-Pérez,Elena Fdez,Belén Fernández,Antonio Ordóñez,Marian Blanca Ramírez,Patricia Gómez-Suaga,Dieter Waschbüsch,Evy Lobbestael,Veerle Baekelandt,Angus C. Nairn,Javier Ruiz-Martínez,Ana Aiastui,Adolfo López de Munain,Pawel Lis,Thomas Comptdaer,Jean-Marc Taymans,Marie-Christine Chartier-Harlin,A Beilina,Adriano Gonnelli,Mark R. Cookson,Elisa Greggio,Sabine Hilfiker +21 more
TL;DR: It is shown that pathogenic LRRK2 causes deficits in centrosomal positioning with effects on neurite outgrowth, cell polarization and directed migration, and which can be detected in peripheral cells derived from L RRK2-PD patients as compared to healthy controls, andWhich are reversed upon LRRk2 kinase inhibition.
Journal ArticleDOI
Let's huddle to prevent a muddle: centrosome declustering as an attractive anticancer strategy
TL;DR: Progress made towards demystifying this riddling cellular tactic and exploiting it for chemotherapeutic purposes are detailed, and a model to highlight the integral role of microtubule dynamicity and the delicate balance of forces on which cancer cells rely for effective centrosome clustering is proposed.
Journal ArticleDOI
CP110 and its network of partners coordinately regulate cilia assembly
TL;DR: This review will mainly focus on recent advances in understanding of the regulatory mechanisms underlying cilia assembly, with special attention paid to the centriolar protein, CP110, its interacting partner Cep290, and the various downstream molecular players and events leading to intraflagellar transport (IFT), a process that mediates the bidirectional movement of protein cargos along the axoneme and that is essential for cilia formation and maintenance.
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Evolutionary cell biology of chromosome segregation: insights from trypanosomes
Bungo Akiyoshi,Keith Gull +1 more
TL;DR: The current understanding of the mitotic mechanism in Trypanosoma brucei, an experimentally tractable kinetoplastid parasite that branched early in eukaryotic history, is reviewed.
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Centrosome dynamics as a source of chromosomal instability.
TL;DR: Novel insights are discussed into the mechanisms that underlie centrosome dynamics and how these mechanisms are perturbed in cancer cells to drive chromosome mis-segregation and advance neoplastic transformation.
References
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The primary cilium: a signalling centre during vertebrate development
TL;DR: The connections between cilia and developmental signalling have begun to clarify the basis of human diseases associated with ciliary dysfunction, and the cilium represents a nexus for signalling pathways during development.
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A Mechanism Linking Extra Centrosomes to Chromosomal Instability
TL;DR: It is demonstrated that cells with multiple centrosomes rarely undergo multipolar cell divisions, and the progeny of these divisions are typically inviable, and it is proposed that this mechanism may be a common underlying cause of CIN in human cancer.
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Proteomic characterization of the human centrosome by protein correlation profiling
Jens S. Andersen,Christopher J. Wilkinson,Thibault Mayor,Thibault Mayor,Peter Mortensen,Erich A. Nigg,Matthias Mann +6 more
TL;DR: 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 identified and validated 23 novel components and identified 41 likely candidates as well as the vast majority of the known centrosomal proteins in a large background of nonspecific proteins.
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Hippo signaling: growth control and beyond
Georg Halder,Randy L. Johnson +1 more
TL;DR: Recently discovered mechanisms that contribute to the dynamic regulation of Hippo signaling during Drosophila and vertebrate development are reviewed and exciting new insights are provided into the elusive mechanisms that regulate organ growth and regeneration.
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Cleavage of Cohesin by the CD Clan Protease Separin Triggers Anaphase in Yeast
TL;DR: It is shown here that separin is a cysteine protease related to caspases that alone can cleave Sccl in vitro and depends on a conserved protein called separin for sister chromatid separation.