The centriole duplication cycle

Fırat-Karalar, Elif Nur; Stearns, Tim

doi:10.1098/rstb.2013.0460

Cited by 134 publications

(111 citation statements)

References 124 publications

(172 reference statements)

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“…Centriole duplication is tightly controlled to avoid supernumerary centrosomes responsible for chromosome segregation defects during mitosis (Firat-Karalar and Stearns 2014). Briefly, at the G 1 /S transition, centrosomal proteins 63 (CEP63) and centrosomal protein 152 (CEP152) form a complex at the proximal end of each centriole, initiating centriole biogenesis (Fig.…”

Section: Molecular Controlmentioning

confidence: 99%

Multiciliated Cells in Animals

Meunier¹,

Azimzadeh²

2016

Cold Spring Harb Perspect Biol

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Many animal cells assemble single cilia involved in motile and/or sensory functions. In contrast, multiciliated cells (MCCs) assemble up to 300 motile cilia that beat in a coordinate fashion to generate a directional fluid flow. In the human airways, the brain, and the oviduct, MCCs allow mucus clearance, cerebrospinal fluid circulation, and egg transportation, respectively. Impairment of MCC function leads to chronic respiratory infections and increased risks of hydrocephalus and female infertility. MCC differentiation during development or repair involves the activation of a regulatory cascade triggered by the inhibition of Notch activity in MCC progenitors. The downstream events include the simultaneous assembly of a large number of basal bodies (BBs)-from which cilia are nucleated-in the cytoplasm of the differentiating MCCs, their migration and docking at the plasma membrane associated to an important remodeling of the actin cytoskeleton, and the assembly and polarization of motile cilia. The direction of ciliary beating is coordinated both within cells and at the tissue level by a combination of planar polarity cues affecting BB position and hydrodynamic forces that are both generated and sensed by the cilia. Herein, we review the mechanisms controlling the specification and differentiation of MCCs and BB assembly and organization at the apical surface, as well as ciliary assembly and coordination in MCCs.

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Section: Molecular Controlmentioning

confidence: 99%

Multiciliated Cells in Animals

Meunier¹,

Azimzadeh²

2016

Cold Spring Harb Perspect Biol

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“…In most proliferating cells, centrioles are duplicated exactly once per cell cycle (Nigg, 2007; Firat‐Karalar & Stearns, 2014). Critical for centriole formation is the assembly of a cartwheel structure onto which nine triplet microtubules are assembled (Gonczy, 2012; Hirono, 2014).…”

Section: Introductionmentioning

confidence: 99%

Quantitative analysis of human centrosome architecture by targeted proteomics and fluorescence imaging

et al. 2016

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Centrioles are essential for the formation of centrosomes and cilia. While numerical and/or structural centrosomes aberrations are implicated in cancer, mutations in centriolar and centrosomal proteins are genetically linked to ciliopathies, microcephaly, and dwarfism. The evolutionarily conserved mechanisms underlying centrosome biogenesis are centered on a set of key proteins, including Plk4, Sas‐6, and STIL, whose exact levels are critical to ensure accurate reproduction of centrioles during cell cycle progression. However, neither the intracellular levels of centrosomal proteins nor their stoichiometry within centrosomes is presently known. Here, we have used two complementary approaches, targeted proteomics and EGFP‐tagging of centrosomal proteins at endogenous loci, to measure protein abundance in cultured human cells and purified centrosomes. Our results provide a first assessment of the absolute and relative amounts of major components of the human centrosome. Specifically, they predict that human centriolar cartwheels comprise up to 16 stacked hubs and 1 molecule of STIL for every dimer of Sas‐6. This type of quantitative information will help guide future studies of the molecular basis of centrosome assembly and function.

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“…Centrosomes generally template their own duplication, and they keep their numbers in check through tight posttranslational regulation of the duplication process itself. Through licensing mechanisms, centrosomal reduplication is prevented, and by virtue of their role in nucleating a bipolar mitotic spindle, centrosomes are faithfully partitioned into each daughter cell at the end of mitosis (2,3).…”

mentioning

confidence: 99%

Epidermal development, growth control, and homeostasis in the face of centrosome amplification

Kulukian

Holland

Vitre

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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As nucleators of the mitotic spindle and primary cilium, centrosomes play crucial roles in equal segregation of DNA content to daughter cells, coordination of growth and differentiation, and transduction of homeostatic cues. Whereas the majority of mammalian cells carry no more than two centrosomes per cell, exceptions to this rule apply in certain specialized tissues and in select disease states, including cancer. Centrosome amplification, or the condition of having more than two centrosomes per cell, has been suggested to contribute to instability of chromosomes, imbalance in asymmetric divisions, and reorganization of tissue architecture; however, the degree to which these conditions are a direct cause of or simply a consequence of human disease is poorly understood. Here we addressed this issue by generating a mouse model inducing centrosome amplification in a naturally proliferative epithelial tissue by elevating Polo-like kinase 4 (Plk4) expression in the skin epidermis. By altering centrosome numbers, we observed multiciliated cells, spindle orientation errors, and chromosome segregation defects within developing epidermis. None of these defects was sufficient to impart a proliferative advantage within the tissue, however. Rather, impaired mitoses led to p53-mediated cell death and contributed to defective growth and stratification. Despite these abnormalities, mice remained viable and healthy, although epidermal cells with centrosome amplification were still appreciable. Moreover, these abnormalities were insufficient to disrupt homeostasis and initiate or enhance tumorigenesis, underscoring the powerful surveillance mechanisms in the skin.

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The centriole duplication cycle

Cited by 134 publications

References 124 publications

Multiciliated Cells in Animals

Multiciliated Cells in Animals

Quantitative analysis of human centrosome architecture by targeted proteomics and fluorescence imaging

Epidermal development, growth control, and homeostasis in the face of centrosome amplification

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