Spindle-Length-Dependent HURP Localization Allows Centrosomes to Control Kinetochore-Fiber Plus-End Dynamics

Dudka, Damian; Castrogiovanni, Cédric; Liaudet, Nicolas; Vassal, Hélène; Meraldi, Patrick

doi:10.1016/j.cub.2019.08.061

Cited by 38 publications

(57 citation statements)

References 80 publications

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“…This is in contrast to somatic cells, as for example reported recently in centrinone-treated RPE1 cells, where centriolar halves are ~50-70% longer than acentrosomal halves (Dudka et al, 2019). The surprising symmetry of acentrosomal and centrosomal spindle halves in the zygote suggests that centrosome-independent pathways play a more important role for spindle assembly and maintenance.…”

Section: Resultsmentioning

confidence: 64%

Non-rodent mammalian zygotes assemble dual spindles despite the presence of paternal centrosomes

Schneider¹,

Ruijter-Villani

Hossain³

et al. 2020

Preprint

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The first mitosis of the mammalian embryo must partition the parental genomes contained in two pronuclei. In rodent zygotes, sperm centrosomes are degraded and, instead, acentriolar microtubule organizing centers and microtubule self-organization guide the assembly of two separate spindles around the genomes. In non-rodent mammals, including human or bovine, centrosomes are inherited from the sperm and have been widely assumed to be active. Whether non-rodent zygotes assemble a single centrosomal spindle around both genomes, or follow the dual spindle self-assembly pathway is unclear. To address this, we investigated spindle assembly in bovine zygotes by systematic immunofluorescence and real-time light-sheet microscopy. We show that two independent spindles form around the parental genomes despite the presence of centrosomes, which had little effect on spindle structure and were only loosely connected to the two spindles. We conclude that the dual spindle assembly pathway is conserved in non-rodent mammals. This could explain whole parental genome loss frequently observed in blastomeres of human IVF embryos.

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Section: Resultsmentioning

confidence: 64%

Non-rodent mammalian zygotes assemble dual spindles despite the presence of paternal centrosomes

Schneider¹,

Ruijter-Villani

Hossain³

et al. 2020

Preprint

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“…DLGAP5/HURP, a K-MT plus-end binding protein gene during mitosis, plays a key role in proliferation and cell cycle progression through spindle assembly [7,[10][11][12]. The previous studies have shown that an increased expression is detected in many cancer types and the tumor cell lines [7,16,[21][22][23].…”

Section: Discussionmentioning

confidence: 99%

“…HURP is highly dynamic, the enrichment in its phosphorylated form at the kinetochore and in its unphosphorylated form at the centrosomes, and tra cking between centrosomes and kinetochores driven by Aurora A-dependent phosphorylation and PP1/PP2A-associated dephosphorylation [11]. Recently, Dudka and his colleagues found that centrosomes also control HURP accumulation on k-bers by setting k-ber length, which it accumulates on k-bers inversely proportionally to half-spindle length [12]. HURP is periodically expressed during the cell cycle and peaks at G2/M, CDK1/cyclin B phosphorylation results in ubiquitination of HURP by SCF and targets it for proteosomal degradation [13].…”

Section: Introductionmentioning

confidence: 99%

Pan-cancer Analysis Combining with Experiments Indicates the Sensitivity of Renal Carcinogenesis to DLGAP5 Expression

Feng

Guo

et al. 2020

Preprint

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Background: Discs large-associated protein 5 (DLGAP5), a kinetochore ﬁbers-binding protein, has been found to function as a oncoprotein in many cancers. However, its expression patterns in normal and cancer tissues across pan-cancer, as well as the cell lines, are far from clear. Methods: Data from genotype-tissue expression (GTEx) and The Cancer Genome Atlas (TCGA) was used to analyze the DLGAP5 expression in normal tissues and cancer cell lines, respectively. The analysis of DLGAP5 expression in cancer tissues and adjacent tissues was based on data from a combined TCGA and GTEx. The associations between the expression, prognosis and cancer immune infiltrates in pan-cancer were also investigated based on TCGA and Tumor Immune Estimation Resource (TIMER), respectively. Furthermore, the analysis results of ccRCC was verified using cell lines via RNAi, western blotting, and the cytological analysis.Results: The low expression levels of DLGAP5 were observed in 31 types of common human tissues, including kidney tissue. However, its expression displayed upregulation in all the 21 tested cancer cell lines, of which kidney cancer cell lines showed a minimal upregulation. As predicted, the significant overexpression of DLGAP5 occurred in at least 26 types of common cancer tissues compared with the adjacent normal tissues. Surprisingly, in three types of kidney cancer (KICH, KIRC/ccRCC, KIRP), DLGAP5 exhibited a statistically significant, but minor, overexpression among 26 types of tested cancers. Furthermore, the survival probability of some tested cancers, including kidney cancer, were significantly related to the upregulated expression of DLGAP5. In addition, among 33 types of tested cancers, KIRC/ccRCC, LGG and LIHC showed a significant positive correlation between DLGAP5 expression and immune infiltration levels. DLGAP5 expression level was also significantly positive correlated with clinical TNM stage of ccRCC patients. Regarding ccRCC tissues and the cell lines, upregulation expression of DLGAP5 was also detected. Its knockdown inhibited the cells viability and proliferation, and compromised the cells migration and invasion. Conclusions: DLGAP5 overexpression occurred in common human cancers, including the kidney cancers. Notably, ccRCC, seemed to be particularly sensitive to the expression. DLGAP5, therefore, may be as a robust independent prognostic biomarker in ccRCC diagnosis.

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“…Centrinone has been used in several studies to investigate the relationship and dependency between the two organelles (Guizzunti and Seemann, 2016;Wu et al, 2016). Moreover, Dudka et al produced human cells which have only one centrosome during mitosis through treatment with centrinone (Dudka et al, 2019). They used these cells as a tool for studying k-fiber dynamics in cells with asymmetric bipolar spindles and found that the centrosome regulated k-fiber plusends in a HURP-dependent manner.…”

Section: Emergence Of Centrinone: a Reversible And Selective Inhibitomentioning

confidence: 99%

Centrosomal and Non-centrosomal Functions Emerged through Eliminating Centrosomes

Takeda

Kuroki

Chinen

et al. 2020

Cell Struct. Funct.

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Centrosomes are highly conserved organelles that act as the major microtubuleorganizing center (MTOC) in animal somatic cells. Through their MTOC activity, centrosomes play various roles throughout the cell cycle, such as supporting cell migration in interphase and spindle organization and positioning in mitosis. Various approaches for removing centrosomes from somatic cells have been developed and applied over the past few decades to understand the precise roles of centrosomes. Centrinone, a reversible and selective PLK4 (polo-like kinase 4) inhibitor, has recently emerged as an efficient approach to eliminate centrosomes. In this review, we describe the latest findings on centrosome function that have been revealed using various centrosome-eliminating approaches. In addition, we discuss our recent findings on the mechanism of centrosome-independent spindle bipolarization, discovered through the use of centrinone.

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Spindle-Length-Dependent HURP Localization Allows Centrosomes to Control Kinetochore-Fiber Plus-End Dynamics

Cited by 38 publications

References 80 publications

Non-rodent mammalian zygotes assemble dual spindles despite the presence of paternal centrosomes

Non-rodent mammalian zygotes assemble dual spindles despite the presence of paternal centrosomes

Pan-cancer Analysis Combining with Experiments Indicates the Sensitivity of Renal Carcinogenesis to DLGAP5 Expression

Centrosomal and Non-centrosomal Functions Emerged through Eliminating Centrosomes

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