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https://www.readbyqxmd.com/read/28516224/psychiatric-behaviors-associated-with-cytoskeletal-defects-in-radial-neuronal-migration
#1
REVIEW
Toshifumi Fukuda, Shigeru Yanagi
Normal development of the cerebral cortex is an important process for higher brain functions, such as language, and cognitive and social functions. Psychiatric disorders, such as schizophrenia and autism, are thought to develop owing to various dysfunctions occurring during the development of the cerebral cortex. Radial neuronal migration in the embryonic cerebral cortex is a complex process, which is achieved by strict control of cytoskeletal dynamics, and impairments in this process are suggested to cause various psychiatric disorders...
May 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28515047/centrosome-amplification-a-suspect-in-breast-cancer-and-racial-disparities
#2
Angela Ogden, Padmashree C G Rida, Ritu Aneja
The multifaceted involvement of centrosome amplification (CA) in tumorigenesis is coming into focus following years of meticulous experimentation, which have elucidated the powerful abilities of CA to promote cellular invasion, disrupt stem cell division, drive chromosomal instability (CIN), and perturb tissue architecture, activities that can accelerate tumor progression. Integration of the extant in vitro, in vivo, and clinical data suggests that in some tissues CA may be a tumor-initiating event, in others a consequential "hit" in multistep tumorigenesis, and in still others non-tumorigenic...
May 17, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28510357/kif11-silencing-and-inhibition-induces-chromosome-instability-that-may-contribute-to-cancer
#3
Yasamin Asbaghi, Laura L Thompson, Zelda Lichtensztejn, Kirk J McManus
Understanding the aberrant pathways that contribute to oncogenesis and identifying the altered genes involved in these pathways is a critical first step to develop effective strategies to better combat cancer. Chromosome instability (CIN) is an aberrant phenotype that occurs in ∼80% of all cancer types and is associated with aggressive tumors, the acquisition of multi-drug resistance and poor patient prognosis. Despite these associations however, the aberrant genes and molecular defects underlying CIN remain poorly understood...
May 16, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28498859/usp9x-counteracts-differential-ubiquitination-of-nphp5-by-march7-and-bbs11-to-regulate-ciliogenesis
#4
Arindam Das, Jin Qian, William Y Tsang
Ciliogenesis is a fundamental biological process central to human health. Precisely how this process is coordinated with the cell cycle remains an open question. We report that nephrocystin-5 (NPHP5/IQCB1), a positive regulator of ciliogenesis, is a stable and low turnover protein subjected to cycles of ubiquitination and deubiquitination. NPHP5 directly binds to a deubiquitinating enzyme USP9X/FAM and two E3 ubiquitin ligases BBS11/TRIM32 and MARCH7/axotrophin. NPHP5 undergoes K63 ubiquitination in a cell cycle dependent manner and K48/K63 ubiquitination upon USP9X depletion or inhibition...
May 12, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28493118/position-matters-multiple-functions-of-linc-dependent-chromosome-positioning-during-meiosis
#5
Kazuhiro Katsumata, Eriko Nishi, Sadia Afrin, Kaoru Narusawa, Ayumu Yamamoto
Chromosome positioning is crucial for multiple chromosomal events, including DNA replication, repair, and recombination. The linker of nucleoskeleton and cytoskeleton (LINC) complexes, which consist of conserved nuclear membrane proteins, were shown to control chromosome positioning and facilitate various biological processes by interacting with the cytoskeleton. However, the precise functions and regulation of LINC-dependent chromosome positioning are not fully understood. During meiosis, the LINC complexes induce clustering of telomeres, forming the bouquet chromosome arrangement, which promotes homologous chromosome pairing...
May 10, 2017: Current Genetics
https://www.readbyqxmd.com/read/28492281/c-elegans-chromosomes-connect-to-centrosomes-by-anchoring-into-the-spindle-network
#6
Stefanie Redemann, Johannes Baumgart, Norbert Lindow, Michael Shelley, Ehssan Nazockdast, Andrea Kratz, Steffen Prohaska, Jan Brugués, Sebastian Fürthauer, Thomas Müller-Reichert
The mitotic spindle ensures the faithful segregation of chromosomes. Here we combine the first large-scale serial electron tomography of whole mitotic spindles in early C. elegans embryos with live-cell imaging to reconstruct all microtubules in 3D and identify their plus- and minus-ends. We classify them as kinetochore (KMTs), spindle (SMTs) or astral microtubules (AMTs) according to their positions, and quantify distinct properties of each class. While our light microscopy and mutant studies show that microtubules are nucleated from the centrosomes, we find only a few KMTs directly connected to the centrosomes...
May 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28488934/the-zebrafish-curly-fry-is-required-for-proper-centrosome-and-mitotic-spindle-assembly
#7
Mi Hye Song, Jeffrey C Medley, John Y Kuwada
The zebrafish curly fry (cfy) mutation leads to a dramatic increase in mitotic index and cell death starting during neural tube formation. The mutant phenotype is cell autonomous and does not result from defects in apical/basal polarity within the neuroepithelium. The increase in mitotic index could be due to increased proliferation or cell cycle arrest in mitosis. cfy embryos were analyzed to examine these two possibilities. By labeling embryos with a pulse of BrdU and anti-phospho-histone 3 and examining the DNA content by fluorescence activated cell sorting, we show that cfy mutants exhibit no increase in proliferation, but a significant increase in the number of cells arrested in mitosis...
May 10, 2017: Zebrafish
https://www.readbyqxmd.com/read/28487562/protein-phosphatase-2a-pp2a-regulates-eg5-to-control-mitotic-progression
#8
Yang Liu, Zhong Zhang, Hui Liang, Xuyang Zhao, Ling Liang, Guangxi Wang, Jingyi Yang, Yan Jin, Michael A McNutt, Yuxin Yin
EG5 (KIF11) is a member of the kinesin-like protein family involved in centrosome separation and bipolar spindle formation. When a cell enters mitosis, CDK1 phosphorylates EG5 at Thr926 and promotes EG5 localization on the mitotic spindle which drives bipolar spindle formation. EG5 provides power for spindle movement and thus controls the dynamics of spindle assembly. However, little is known about EG5 regulation or how EG5 detaches from the spindle upon mitotic exit. In this study we identify EG5 as a novel substrate of PP2A phosphatase, and we show that the PP2A/B55α complex plays an important role in mitotic exit by a mechanism involving EG5...
May 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28476861/the-centrioles-centrosomes-basal-bodies-and-cilia-of-drosophila-melanogaster
#9
Ramona Lattao, Levente Kovács, David M Glover
Centrioles play a key role in the development of the fly. They are needed for the correct formation of centrosomes, the organelles at the poles of the spindle that can persist as microtubule organizing centers (MTOCs) into interphase. The ability to nucleate cytoplasmic microtubules (MTs) is a property of the surrounding pericentriolar material (PCM). The centriole has a dual life, existing not only as the core of the centrosome but also as the basal body, the structure that templates the formation of cilia and flagellae...
May 2017: Genetics
https://www.readbyqxmd.com/read/28475000/effect-of-nima-related-kinase-2b-on-the-sensitivity-of-breast-cancer-to-paclitaxel-in-vitro-and-vivo
#10
Yahong Wang, Honghong Shen, Quangui Yin, Tongxian Zhang, Ziyu Liu, Wei Zhang, Yun Niu
NIMA-related kinase 2B has been known to be an important centrosome regulatory factor. The aim of this study was to investigate the effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel. We detected the expression of NIMA-related kinase 2B messenger RNA in MCF-10 cells, including MCF-10A, MCF-10AT, MCF-10DCIS.com , and MCF-10CA1a. The influence of NIMA-related kinase 2B in nude mouse was also detected. The association between NIMA-related kinase 2B and clinicopathological factors was explored in invasive ductal carcinoma tissues...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28474672/stat3-regulates-centrosome-clustering-in-cancer-cells-via-stathmin-plk1
#11
Edward J Morris, Eiko Kawamura, Jordan A Gillespie, Aruna Balgi, Nagarajan Kannan, William J Muller, Michel Roberge, Shoukat Dedhar
Cancer cells frequently have amplified centrosomes that must be clustered together to form a bipolar mitotic spindle, and targeting centrosome clustering is considered a promising therapeutic strategy. A high-content chemical screen for inhibitors of centrosome clustering identified Stattic, a Stat3 inhibitor. Stat3 depletion and inhibition in cancer cell lines and in tumours in vivo caused significant inhibition of centrosome clustering and viability. Here we describe a transcription-independent mechanism for Stat3-mediated centrosome clustering that involves Stathmin, a Stat3 interactor involved in microtubule depolymerization, and the mitotic kinase PLK1...
May 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28469279/spindle-pole-cohesion-requires-glycosylation-mediated-localization-of-numa
#12
Jérémy Magescas, Lucie Sengmanivong, Amandine Viau, Adeline Mayeux, Tien Dang, Martine Burtin, Ulf J Nilsson, Hakon Leffler, Françoise Poirier, Fabiola Terzi, Delphine Delacour
Glycosylation is critical for the regulation of several cellular processes. One glycosylation pathway, the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) has been shown to be required for proper mitosis, likely through a subset of proteins that are O-GlcNAcylated during metaphase. As lectins bind glycosylated proteins, we asked if specific lectins interact with mitotic O-GlcNAcylated proteins during metaphase to ensure correct cell division. Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28468979/increased-lateral-microtubule-contact-at-the-cell-cortex-is-sufficient-to-drive-mammalian-spindle-elongation
#13
Joshua Guild, Miriam B Ginzberg, Christina L Hueschen, Timothy J Mitchison, Sophie Dumont
The spindle is a dynamic structure that changes its architecture and size in response to biochemical and physical cues. For example, a simple physical change, cell confinement, can trigger centrosome separation and increase spindle steady-state length at metaphase. How this occurs is not understood, and is the question we pose here. We find that metaphase and anaphase spindles elongate at the same rate when confined, suggesting that similar elongation forces can be generated independent of biochemical and spindle structural differences...
May 3, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28465207/characterization-of-sgo1-expression-in-developing-and-adult-mouse
#14
Andrew T Song, Antonella Galli, Severine Leclerc, Stanley Nattel, Craig Mandato, Gregor Andelfinger
SGO1 has been characterized in its function in correct cell division and its role in centrosome cohesion in the nucleus. However, its organ-specific maturation-related expression pattern in vivo remains largely uncharacterized. Here, we show clear SGO1 expression in post-developmental neuronal cells and cytoplasmic localisation in nucleated cells with a transgenic mice model and immunohistochemistry of wild type mice. We demonstrate extranuclear expression of Sgo1 in the developing heart and gut, which have been shown to be dysregulated in humans with homozygous SGO1 mutation...
April 29, 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/28457629/mosaicism-in-preimplantation-human-embryos-when-chromosomal-abnormalities-are-the-norm
#15
REVIEW
Rajiv C McCoy
Along with errors in meiosis, mitotic errors during post-zygotic cell division contribute to pervasive aneuploidy in human embryos. Relatively little is known, however, about the genesis of these errors or their fitness consequences. Rapid technological advances are helping to close this gap, revealing diverse molecular mechanisms contributing to mitotic error. These include altered cell cycle checkpoints, aberrations of the centrosome, and failed chromatid cohesion, mirroring findings from cancer biology. Recent studies are challenging the idea that mitotic error is abnormal, emphasizing that the fitness impacts of mosaicism depend on its scope and severity...
April 27, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28454331/centrosome-amplification-in-chondrosarcomas-a-primary-cell-culture-and-cryopreserved-tumor-sample-study
#16
Carla Aparecida Pinheiro, Iberê Cauduro Soares, Valter Penna, Jeremy Squire, Rui Manuel Vieira Reis, Sandra Regina Morini da Silva, Isabela de Carvalho, Marjori Leiva Camparoto, Maicon Fernando Zanon da Silva, Adhemar Longatto Longatto Filho
The genetics background underlying the aggressiveness of chondrosarcoma (CS) is poorly understood. One possible cause of malignant transformation is chromosomal instability, which involves an error in mitotic segregation due to numerical and/or functional abnormalities of centrosomes. The present study aimed to evaluate centrosome amplification in cryopreserved samples of tumor tissue from patients with CS. An analysis was performed on 3 primary cultures of tumors from patients who underwent surgery between January 2012 and December 2012 at the Department of Orthopedics at the Barretos Cancer Hospital (Barretos, Brazil)...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454295/nima-related-kinase-2-regulates-hepatocellular-carcinoma-cell-growth-and-proliferation
#17
Xiao-Bo Lai, Yu-Qiang Nie, Hong-Li Huang, Ying-Fei Li, Chuang-Yu Cao, Hui Yang, Bo Shen, Zhi-Qiang Feng
NIMA-related kinase 2 (Nek2) is often upregulated in human cancer and is important in regulating the cell cycle and gene expression, and maintaining centrosomal structure and function. The present study aimed to investigate the expression pattern, clinical significance, and biological function of Nek2 in hepatocellular carcinoma (HCC). mRNA and protein levels of Nek2 were examined in HCC and corresponding normal liver tissues. The MTT and soft agar colony formation assays, and flow cytometry were employed to assess the roles of Nek2 in cell proliferation and growth...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28450740/the-centrosomal-ofd1-protein-interacts-with-the-translation-machinery-and-regulates-the-synthesis-of-specific-targets
#18
Daniela Iaconis, Maria Monti, Mario Renda, Arianne van Koppen, Roberta Tammaro, Marco Chiaravalli, Flora Cozzolino, Paola Pignata, Claudia Crina, Piero Pucci, Alessandra Boletta, Vincenzo Belcastro, Rachel H Giles, Enrico Maria Surace, Simone Gallo, Mario Pende, Brunella Franco
Protein synthesis is traditionally associated with specific cytoplasmic compartments. We now show that OFD1, a centrosomal/basal body protein, interacts with components of the Preinitiation complex of translation (PIC) and of the eukaryotic Initiation Factor (eIF)4F complex and modulates the translation of specific mRNA targets in the kidney. We demonstrate that OFD1 cooperates with the mRNA binding protein Bicc1 to functionally control the protein synthesis machinery at the centrosome where also the PIC and eIF4F components were shown to localize in mammalian cells...
April 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28450458/the-mitotic-exit-network-regulates-spindle-pole-body-selection-during-sporulation-of-saccharomyces-cerevisiae
#19
Christian Renicke, Ann-Katrin Allmann, Anne Pia Lutz, Thomas Heimerl, Christof Taxis
Age-based inheritance of centrosomes in eukaryotic cells is associated with faithful chromosome distribution in asymmetric cell divisions. During Saccharomyces cerevisiae ascospore formation, such an inheritance mechanism targets the yeast centrosome equivalents, the spindle pole bodies at meiosis II onset. Decreased nutrient availability causes initiation of spore formation at only the younger spindle pole bodies and their associated genomes. This mechanism ensures encapsulation of non-sister genomes, which preserves genetic diversity and provides a fitness advantage at population level...
April 26, 2017: Genetics
https://www.readbyqxmd.com/read/28448044/generation-of-ipsc-derived-human-brain-organoids-to-model-early-neurodevelopmental-disorders
#20
Elke Gabriel, Jay Gopalakrishnan
The restricted availability of suitable in vitro models that can reliably represent complex human brain development is a significant bottleneck that limits the translation of basic brain research into clinical application. While induced pluripotent stem cells (iPSCs) have replaced the ethically questionable human embryonic stem cells, iPSC-based neuronal differentiation studies remain descriptive at the cellular level but fail to adequately provide the details that could be derived from a complex, 3D human brain tissue...
April 14, 2017: Journal of Visualized Experiments: JoVE
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