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https://www.readbyqxmd.com/read/28427147/brca1-controls-the-cell-division-axis-and-governs-ploidy-and-phenotype-in-human-mammary-cells
#1
Zhengcheng He, Nagarajan Kannan, Oksana Nemirovsky, Helen Chen, Marisa Connell, Brian Taylor, Jihong Jiang, Linda M Pilarski, Markus C Fleisch, Dieter Niederacher, Miguel Angel Pujana, Connie J Eaves, Christopher A Maxwell
BRCA1 deficiency may perturb the differentiation hierarchy present in the normal mammary gland and is associated with the genesis of breast cancers that are genomically unstable and typically display a basal-like transcriptome. Oriented cell division is a mechanism known to regulate cell fates and to restrict tumor formation. We now show that the cell division axis is altered following shRNA-mediated BRCA1 depletion in immortalized but non-tumorigenic, or freshly isolated normal human mammary cells with graded consequences in progeny cells that include aneuploidy, perturbation of cell polarity in spheroid cultures, and a selective loss of cells with luminal features...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424932/inverse-relationship-of-ca-2-dependent-flagellar-response-between-animal-sperm-and-prasinophyte-algae
#2
Kogiku Shiba, Kazuo Inaba
Symmetry/asymmetry conversion of eukaryotic flagellar waveform is caused by the changes in intracellular Ca(2+). Animal sperm flagella show symmetric or asymmetric waveform at lower or higher concentration of intracellular Ca(2+), respectively. In Chlamydomonas, high Ca(2+) induces conversion of flagellar waveform from asymmetric to symmetry, resulting in the backward movement. This mirror image relationship between animal sperm and Chlamydomonas could be explained by the distinct calcium sensors used to regulate the outer arm dyneins (Inaba 2015)...
April 19, 2017: Journal of Plant Research
https://www.readbyqxmd.com/read/28414272/regulation-of-mitochondria-dynactin-interaction-and-mitochondrial-retrograde-transport-in-axons
#3
Catherine M Drerup, Amy L Herbert, Kelly R Monk, Alex V Nechiporuk
Mitochondrial transport in axons is critical for neural circuit health and function. While several proteins have been found that modulate bidirectional mitochondrial motility, factors that regulate unidirectional mitochondrial transport have been harder to identify. In a genetic screen, we found a zebrafish strain in which mitochondria fail to attach to the dynein retrograde motor. This strain carries a loss-of-function mutation in actr10, a member of the dynein-associated complex dynactin. The abnormal axon morphology and mitochondrial retrograde transport defects observed in actr10 mutants are distinct from dynein and dynactin mutant axonal phenotypes...
April 17, 2017: ELife
https://www.readbyqxmd.com/read/28414126/characterization-of-the-novel-protein-kiaa0564-von-willebrand-domain-containing-protein-8
#4
Moulun Luo, April E Mengos, Wuqiong Ma, Jean Finlayson, Rocio Zapata Bustos, Yuan Xiao Zhu, Chang-Xin Shi, Tianna M Stubblefield, Wayne T Willis, Lawrence J Mandarino
The VWA8 gene was first identified by the Kazusa cDNA project and named KIAA0564. Based on the observation, by similarity, that the protein encoded by KIAA0564 contains a Von Willebrand Factor 8 domain, KIAA0564 was named Von Willebrand Domain-containing Protein 8 (VWA8). The function of VWA8 protein is almost unknown. The purpose of this study was to characterize the tissue distribution, cellular location, and function of VWA8. In mice VWA8 protein was mostly distributed in liver, kidney, heart, pancreas and skeletal muscle, and is present as a long isoform and a shorter splice variant (VWA8a and VWA8b)...
April 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28410195/antagonistic-effects-of-selenium-on-lead-induced-autophagy-by-influencing-mitochondrial-dynamics-in-the-spleen-of-chickens
#5
Yujing Han, Chunqiu Li, Mingjun Su, Zhihui Wang, Ning Jiang, Dongbo Sun
Lead (Pb) may damage the immune function in human and animal. Selenium (Se) has antagonistic effects on Pb. In our study, brown layer chickens were randomly allocated to control group, Se group (1 mg/kg Se), Se+Pb group (1 mg/kg Se and 350 mg/kg Pb), and Pb group (350 mg/kg Pb). The chickens were sacrificed on the 90th day; spleen tissues were subjected to observation of ultrastructure and detection of spleen-related indexes. The results revealed that in the Pb group, expression levels of the cytokines IL-1 and TNF-α significantly increased, and expression levels of IL-2 and INF-γ significantly decreased; activities of antioxidant enzyme GPX, SOD and CAT significantly decreased, and expression level of malondialdehyde (MDA) significantly increased; expression levels of mitochondrial fission-related genes (Mff and Drp1) significantly increased, and expression levels of mitochondrial fusion-related genes (Opa1, Mfn1 and Mfn2) significantly decreased; expression of autophagy-related genes (Beclin 1, Dynein, Atg 5, LC3-I and LC-II) was upregulated, while expression of mammalian target of rapamycin (mTOR) was downregulated...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410148/remodeling-of-tick-cytoskeleton-in-response-to-infection-with-anaplasma-phagocytophilum
#6
Alejandro Cabezas-Cruz, Pilar Alberdi, James J Valdes, Margarita Villar, Jose de la Fuente
The obligate intracellular pathogen Anaplasma phagocytophilum infects vertebrate and tick hosts. In this study, a genome-wide search for cytoskeleton components was performed in the tick vector, Ixodes scapularis. The available transcriptomics and proteomics data was then used to characterize the mRNA and protein levels of I. scapularis cytoskeleton components in response to A. phagocytophilum infection. The results showed that cytoskeleton components described in other model organisms were present in the I...
June 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28409085/mechanical-properties-of-spindle-poles-are-symmetrically-balanced
#7
Kazuya Suzuki, Takeshi Itabashi, Shin'ichi Ishiwata
The metaphase spindle is organized for accurate chromosome segregation. One of the fundamental features of the spindle across the species is its symmetrical shape; the spindle consists of two polar arrays of microtubules at both ends. Although it has been suggested that the formation of the bipolar shape requires force balance coordination by molecular motors, i.e., kinesins and dyneins, quantitative analysis for the pole mechanics has not been conducted. Here, we demonstrate that it is not only the shape but also the stiffness and microtubule density of the pairs of pole regions are symmetrically balanced in single spindles self-assembled in Xenopus egg extracts...
2017: Biophysics and Physicobiology
https://www.readbyqxmd.com/read/28406398/lissencephaly-1-is%C3%A2-a-context-dependent-regulator%C3%A2-of-the-human-dynein-complex
#8
Janina Baumbach, Andal Murthy, Mark A McClintock, Carly I Dix, Ruta Zalyte, Ha Thi Hoang, Simon L Bullock
The cytoplasmic dynein-1 (dynein) motor plays a central role in microtubule organisation and cargo transport. These functions are spatially regulated by association of dynein and its accessory complex dynactin with dynamic microtubule plus ends. Here, we elucidate in vitro the roles of dynactin, end-binding protein-1 (EB1) and Lissencephaly-1 (LIS1) in the interaction of end tracking and minus end-directed human dynein complexes with these sites. LIS1 promotes dynactin-dependent tracking of dynein on both growing and shrinking plus ends...
April 13, 2017: ELife
https://www.readbyqxmd.com/read/28406181/local-inhibition-of-microtubule-dynamics-by-dynein-is-required-for-neuronal-cargo-distribution
#9
Shaul Yogev, Celine I Maeder, Roshni Cooper, Mark Horowitz, Adam G Hendricks, Kang Shen
Abnormal axonal transport is associated with neuronal disease. We identified a role for DHC-1, the C. elegans dynein heavy chain, in maintaining neuronal cargo distribution. Surprisingly, this does not involve dynein's role as a retrograde motor in cargo transport, hinging instead on its ability to inhibit microtubule (MT) dynamics. Neuronal MTs are highly static, yet the mechanisms and functional significance of this property are not well understood. In disease-mimicking dhc-1 alleles, excessive MT growth and collapse occur at the dendrite tip, resulting in the formation of aberrant MT loops...
April 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28405357/nonlinear-amplitude-dynamics-in-flagellar-beating
#10
David Oriola, Hermes Gadêlha, Jaume Casademunt
The physical basis of flagellar and ciliary beating is a major problem in biology which is still far from completely understood. The fundamental cytoskeleton structure of cilia and flagella is the axoneme, a cylindrical array of microtubule doublets connected by passive cross-linkers and dynein motor proteins. The complex interplay of these elements leads to the generation of self-organized bending waves. Although many mathematical models have been proposed to understand this process, few attempts have been made to assess the role of dyneins on the nonlinear nature of the axoneme...
March 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/28402699/inhibition-of-retrograde-transport-modulates-misfolded-protein-accumulation-and-clearance-in-motoneuron-diseases
#11
Riccardo Cristofani, Valeria Crippa, Paola Rusmini, Maria Elena Cicardi, Marco Meroni, Nausicaa V Licata, Gessica Sala, Elisa Giorgetti, Christopher Grunseich, Mariarita Galbiati, Margherita Piccolella, Elio Messi, Carlo Ferrarese, Serena Carra, Angelo Poletti
Motoneuron diseases, like spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS), are associated with proteins that because of gene mutation or peculiar structures, acquire aberrant (misfolded) conformations toxic to cells. To prevent misfolded protein toxicity, cells activate a protein quality control (PQC) system composed of chaperones and degradative pathways (proteasome and autophagy). Inefficient activation of the PQC system results in misfolded protein accumulation that ultimately leads to neuronal cell death, while efficient macroautophagy/autophagy-mediated degradation of aggregating proteins is beneficial...
April 12, 2017: Autophagy
https://www.readbyqxmd.com/read/28395407/-the-clinical-characteristics-of-17-cases-of-primary-ciliary-dyskinesia
#12
X L Tian, S B Wang, S Y Zheng, X Li, K F Xu
Objective: To review the clinical data of cases of primary ciliary dyskinesia (PCD), and to explore the clinical characteristics for the understanding of PCD. Methods: We retrospectively summarized 17 patients with PCD diagnosed in Peking Union Medical College Hospital from Jan 2009 to Dec 2014. There were 7 male and 10 female patients, with the age from 6 to 57 years at the time of diagnosis. The mean onset age of the disease was 11.7±2.1 years, and the mean age at diagnosis was 29.5±3.5 years. We analyzed their clinical symtoms, radiologic images, pulmonary function test and the electron microscopic findings for the clinical characteristics of PCD...
April 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28395088/neuropathological-hallmarks-of-brain-malformations-in-extreme-phenotypes-related-to-dync1h1-mutations
#13
Annie Laquerriere, Camille Maillard, Mara Cavallin, Françoise Chapon, Florent Marguet, Arnaud Molin, Sabine Sigaudy, Marie Blouet, Guillaume Benoist, Carla Fernandez, Karine Poirier, Jamel Chelly, Sophie Thomas, Nadia Bahi-Buisson
Dyneins play a critical role in a wide variety of cellular functions such as the movement of organelles and numerous aspects of mitosis, making it central player in neocortical neurogenesis and migration. Recently, cytoplasmic dynein-1, heavy chain-1 (DYNC1H1) mutations have been found to cause a wide spectrum of brain cortical malformations. We report on the detailed neuropathological features of brain lesions from 2 fetuses aged 36 and 22 weeks of gestation (WG), respectively, carrying de novo DYNC1H1 mutations, p...
March 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28394326/intraflagellar-transport-dynein-is-autoinhibited-by-trapping-of-its-mechanical-and-track-binding-elements
#14
Katerina Toropova, Miroslav Mladenov, Anthony J Roberts
Cilia are multifunctional organelles that are constructed using intraflagellar transport (IFT) of cargo to and from their tip. It is widely held that the retrograde IFT motor, dynein-2, must be controlled in order to reach the ciliary tip and then unleashed to power the return journey. However, the mechanism is unknown. Here, we systematically define the mechanochemistry of human dynein-2 motors as monomers, dimers, and multimotor assemblies with kinesin-II. Combining these data with insights from single-particle EM, we discover that dynein-2 dimers are intrinsically autoinhibited...
April 10, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28389272/characterization-of-ciliobrevin-a-mediated-dynein-atpase-inhibition-on-flagellar-motility-of-leishmania-donovani
#15
G Srinivas Reddy, Aakash Gautam Mukhopadhyay, Chinmoy Sankar Dey
Axonemal dyneins are members of AAA+ proteins involved in force generation and are responsible for flagellar motility in eukaryotes. In this study, we characterized the effects of ciliobrevin A (CbA), a dynein ATPase inhibitor, on flagella driven motility of the protozoan parasite Leishmania donovani. Using fast-capture video microscopy, we observed that CbA decreased flagellar beat frequency of swimming parasites in a concentration-dependent manner. Beat frequency of live and reactivated L. donovani decreased by approximately 89% and 41% respectively in the presence of 250μM CbA...
April 5, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28386021/camsap3-accumulates-in-the-pericentrosomal-area-and-accompanies-microtubules-release-from-the-centrosome-via-katanin
#16
Congcong Dong, Honglin Xu, Rui Zhang, Nobutoshi Tanaka, Masatoshi Takeichi, Wenxiang Meng
The epithelium has apico-basal axis polarity that plays an important role in absorption, excretion and other physiological functions. In epithelial cells, a substantial number of noncentrosomal microtubules (MTs) are scattered in the cytoplasm with an apico-basal polarity to adapt to these complex functions. Several previous studies have found that noncentrosomal MTs are nucleated at the centrosome, and then released and translocated elsewhere. However, the detailed process and molecular mechanism remains largely unknown...
April 6, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28380337/what-s-in-an-average-an-ensemble-view-of-phosphorylation-effects
#17
Alexander F Chin, Vincent J Hilser
The number of examples of functional post-translational modulation of disordered proteins rapidly grows. In a recent issue of Structure, Jie et al. (2017) show that phosphorylation of dynein intermediate chain alters partner binding but retains its dynamic, disorder character. An ensemble model offers an organizing framework to relate function, conformation, and phosphorylation in disordered and ordered proteins alike.
April 4, 2017: Structure
https://www.readbyqxmd.com/read/28379358/loss-of-dynein-2-intermediate-chain-wdr34-results-in-defects-in-retrograde-ciliary-protein-trafficking-and-hedgehog-signaling-in-the-mouse
#18
Chuanqing Wu, Jia Li, Andrew Peterson, Kaixiong Tao, Baolin Wang
The Wdr34 gene encodes an intermediate chain of cytoplasmic dynein 2, the motor for retrograde intraflagellar transport (IFT) in primary cilia. Although mutations in human WDR34 have recently been reported, the association of WDR34 function with Hedgehog (Hh) signaling has not been established, and actual cilia defects in the WDR34 mutant cells have also not been completely characterized. In the present study, we show that Wdr34 mutant mice die in midgestation and exhibit open brain and polydactyly phenotypes...
March 31, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28368306/icam-1-binding-rhinoviruses-enter-hela-cells-via-multiple-pathways-and-travel-to-distinct-intracellular-compartments-for-uncoating
#19
Haleh Ganjian, Christin Zietz, Diana Mechtcheriakova, Dieter Blaas, Renate Fuchs
Of the more than 150 human rhinovirus (RV) serotypes, 89 utilize intercellular adhesion molecule-1 (ICAM-1) for cell entry. These belong either to species A or B. We recently demonstrated that RV-B14 and RV-A89, despite binding this same receptor, are routed into distinct endosomal compartments for release of their RNA into the cytosol. To gain insight into the underlying mechanism we now comparatively investigate the port of entry, temperature-dependence of uncoating, and intracellular routing of RV-B3, RV-B14, RV-A16, and RV-A89 in HeLa cells...
April 1, 2017: Viruses
https://www.readbyqxmd.com/read/28367102/inhibition-of-proteasome-activity-induces-aggregation-of-ifit2-in-the-centrosome-and-enhances-ifit2-induced-cell-apoptosis
#20
Limin Chen, Shuyuan Liu, Fen Xu, Yunyuan Kong, Lagen Wan, Yonglu Zhang, Zhanglin Zhang
IFN-induced protein with tetratricopeptide repeats 2 (IFIT2), one of the most highly responsive interferon-stimulated genes, inhibits the proliferation and migration of cancer cells and regulates viral replication. IFIT2 has been demonstrated to be a cytoskeleton-associated protein that becomes enriched in the mitotic spindle of cells. However, the molecular mechanisms by which IFIT2 executes biological functions are largely unclear. The findings of this study showed that inhibiting the activation of proteasome led to the enrichment of IFIT2 and induced the aggregation of IFIT2 protein in the centrosome...
2017: International Journal of Biological Sciences
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