Cep126 is required for pericentriolar satellite localisation to the centrosome and for primary cilium formation

Bonavita, Raffaella; Walas, Dawid; Brown, Anna K.; Luini, Alberto; Stephens, David; Colanzi, Antonino

doi:10.1111/boc.201300087

Cited by 15 publications

(12 citation statements)

References 27 publications

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“…The term pericentriolar satellite defines electron-dense granules around the centrosome. These granules recruit centrosomal proteins and have functions in cilia formation [ 31 , 32 ]. In C-Nap1 KO cells the pericentriolar satellite protein PCM-1 [ 33 ] was preferentially positioned towards the Cep164-marked mother centriole ( S1A – S1C Fig).…”

Section: Resultsmentioning

confidence: 99%

The Centrosomal Linker and Microtubules Provide Dual Levels of Spatial Coordination of Centrosomes

et al. 2015

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The centrosome is the principal microtubule organizing center in most animal cells. It consists of a pair of centrioles surrounded by pericentriolar material. The centrosome, like DNA, duplicates exactly once per cell cycle. During interphase duplicated centrosomes remain closely linked by a proteinaceous linker. This centrosomal linker is composed of rootletin filaments that are anchored to the centrioles via the protein C-Nap1. At the onset of mitosis the linker is dissolved by Nek2A kinase to support the formation of the bipolar mitotic spindle. The importance of the centrosomal linker for cell function during interphase awaits characterization. Here we assessed the phenotype of human RPE1 C-Nap1 knockout (KO) cells. The absence of the linker led to a modest increase in the average centrosome separation from 1 to 2.5 μm. This small impact on the degree of separation is indicative of a second level of spatial organization of centrosomes. Microtubule depolymerisation or stabilization in C-Nap1 KO cells dramatically increased the inter-centrosomal separation (> 8 μm). Thus, microtubules position centrosomes relatively close to one another in the absence of linker function. C-Nap1 KO cells had a Golgi organization defect with a two-fold expansion of the area occupied by the Golgi. When the centrosomes of C-Nap1 KO cells showed considerable separation, two spatially distinct Golgi stacks could be observed. Furthermore, migration of C-Nap1 KO cells was slower than their wild type RPE1 counterparts. These data show that the spatial organization of centrosomes is modulated by a combination of centrosomal cohesion and microtubule forces. Furthermore a modest increase in centrosome separation has major impact on Golgi organization and cell migration.

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Section: Resultsmentioning

confidence: 99%

The Centrosomal Linker and Microtubules Provide Dual Levels of Spatial Coordination of Centrosomes

et al. 2015

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“…These include CCDC11 [30], CCDC12 [26], CCDC13 [50], CCDC14 [23, 26], CCDC18 [26], CCDC66 [26], CEP63 [23, 51–53], CEP72 [54], CEP90 [55, 56], CEP126 [57], CEP131/AZI1 [26, 58–60], CEP290 (also called NPHP6) [38, 61–63], FOR20 [64], HAP1 and HTT [36, 65], KIAA0753 [23], Par6α [66] and SDCCAG8 [67]. However, in most of these cases, the underlying molecular mechanisms by which centriolar satellite integrity is disturbed have not yet been explored, and it remains to be determined whether alterations of centriolar satellite distributions are due to the failure of PCM1 oligomerisation, the compromised interaction of PCM1 with other components or perturbation of the association of PCM1 particles with microtubules (see below).…”

Section: Intrinsic Control Of Centriolar Satellite Integritymentioning

confidence: 99%

Regulation of centriolar satellite integrity and its physiology

Hori

Toda

2016

Cell. Mol. Life Sci.

108

140

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Centriolar satellites comprise cytoplasmic granules that are located around the centrosome. Their molecular identification was first reported more than a quarter of a century ago. These particles are not static in the cell but instead constantly move around the centrosome. Over the last decade, significant advances in their molecular compositions and biological functions have been achieved due to comprehensive proteomics and genomics, super-resolution microscopy analyses and elegant genetic manipulations. Centriolar satellites play pivotal roles in centrosome assembly and primary cilium formation through the delivery of centriolar/centrosomal components from the cytoplasm to the centrosome. Their importance is further underscored by the fact that mutations in genes encoding satellite components and regulators lead to various human disorders such as ciliopathies. Moreover, the most recent findings highlight dynamic structural remodelling in response to internal and external cues and unexpected positive feedback control that is exerted from the centrosome for centriolar satellite integrity.

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“…Candidate genes identified in this region were related to both cell division (Centrosomal Protein 126 (CEP126)) and immune cell progenitor differentiation (Angiopoietin Like 5 (ANGPTL5)), suggesting that Risk PC1 does indeed reflect both mastitis and udder and teat morphology (16,17). (26).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide associations for udder and teat conformational risk factors for mastitis in Holstein cows

Miles¹,

Posbergh²,

Huson³

2019

Preprint

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BACKGROUND The objective of our study was to conduct high-density genome-wide association studies of dairy cow udder and teat conformation with direct phenotyping. We identified and compared quantitative trait loci ( QTL ) for a novel composite mastitis risk trait and considered environmental impact of milking by comparing primiparous cows only. Cows (N = 471) were genotyped on the Illumina BovineHD 777K beadchip and scored for front and rear teat length, width, end shape, and placement, fore udder attachment, udder cleft, udder depth, rear udder height, and rear udder width. Principal component analysis was performed on fore udder attachment, rear teat end shape, rear teat width, and rear udder height, to create a single new phenotype describing mastitis susceptibility based on these high-risk traits.RESULTS Over all 14 traits of interest, a total of 56 genome-wide associations were performed and 28 significantly associated (Bonferroni multiple testing correction < 0.05) QTL were identified. The linkage disequilibrium ( LD ) block surrounding the associated QTL or a 1 Mb window in the absence of LD was interrogated for candidate genes, resulting in the identification of genes with functions related to both cell proliferation and immune signaling, including ZNF683, DHX9, CUX1, TNNT1 , and SPRY1 . We assessed a primiparous only subset of cows (n = 144) to account for the possibility that the genetic variance component of the phenotype is greater for cows who have had less exposure to the environment, and observed different associated QTL and inheritance patterns for udder depth in primiparous cows compared to the total cohort.CONCLUSION Special focus was given to the aforementioned mastitis risk traits, and candidate gene investigation revealed both immune function and cell proliferation related genes in the areas surrounding significantly associated QTL, suggesting that selecting for mastitis resistant cows based on these traits would be an effective method for increasing mastitis resiliency in a herd.

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Cep126 is required for pericentriolar satellite localisation to the centrosome and for primary cilium formation

Cited by 15 publications

References 27 publications

The Centrosomal Linker and Microtubules Provide Dual Levels of Spatial Coordination of Centrosomes

The Centrosomal Linker and Microtubules Provide Dual Levels of Spatial Coordination of Centrosomes

Regulation of centriolar satellite integrity and its physiology

Genome-wide associations for udder and teat conformational risk factors for mastitis in Holstein cows

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