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Tubulin

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https://www.readbyqxmd.com/read/28643946/activated-proline-rich-tyrosine-kinase-2-regulates-meiotic-spindle-assembly-in-the-mouse-oocyte
#1
Xiao-Qian Meng, Bing Cui, Dong Cheng, Hui Lyu, Li-Gang Jiang, Ke-Gang Zheng, Shu-Zhen Liu, Jie Pan, Cong Zhang, Jing Bai, Jun Zhou
Proline-rich tyrosine kinase 2 (PYK2), a member of the protein tyrosine kinase family, plays an important role in various cellular processes. PYK2 can be phosphorylated on tyrosine 402 by diverse stimuli at the cell surface, and recent studies have shown that this activated form of PYK2 is enriched in oocytes and required for fertilization. However, the subcellular localization and functions of activated PYK2 in oocytes remain elusive. In this study, we demonstrate that the localization of p-PYK2 undergoes dynamic changes during in vitro maturation of mouse oocytes...
June 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28640995/colloidal-gold-nanoparticles-induce-changes-in-cellular-and-subcellular-morphology
#2
Xiaowei Ma, Raimo Hartmann, Dorleta Jimenez de Aberasturi, Fang Yang, Stefaan J H Soenen, Bella B Manshian, Jonas Franz, Daniel Valdeperez, Beatriz Pelaz, Neus Feliu, Norbert Hampp, Christoph Riethmüller, Henning Vieker, Natalie Frese, Armin Gölzhäuser, Michael Simonich, Robert L Tanguay, Xing-Jie Liang, Wolfgang J Parak
Exposure of cells to colloidal nanoparticles (NPs) can have concentration-dependent harmful effects. Mostly, such effects are monitored with biochemical assays or probes from molecular biology, i.e. viability assays, gene expression profiles, etc., neglecting that the presence of NPs can also drastically affect cellular morphology. In the case of polymer-coated Au NPs we demonstrate that upon NP internalization, cells undergo lysosomal swelling, alterations in mitochondrial morphology, disturbances in actin and tubulin cytoskeleton and associated signaling, and reduction of focal adhesion contact area and number of filopodia...
June 22, 2017: ACS Nano
https://www.readbyqxmd.com/read/28640948/high-level-%C3%AE-iii-tubulin-overexpression-occurs-in-most-head-and-neck-cancers-but-is-unrelated-to-clinical-outcome
#3
Julie C Nienstedt, Alexander Gröbe, Till Clauditz, Ronald Simon, Adrian Muenscher, Rainald Knecht, Guido Sauter, Christoph Moebius, Marco Blessmann, Max Heiland, Christina Pflug
BACKGROUND: βIII-tubulin (TUBB3) is an isotype of microtubules, which are involved in crucial cellular roles including maintenance of cell shape, intracellular transport, and mitosis. Overexpression of TUBB3 was found to be associated with poor prognosis and resistance to tubulin-binding drugs and in several solid tumors including head and neck squamous cell carcinomas (HNSCC). Considering the potential high importance of a prognostic biomarker in these cancers, the present study aimed to investigate the clinical relevance of immunohistochemical TUBB3 expression in HNSCC...
June 22, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28640849/motility-in-blastogregarines-apicomplexa-native-and-drug-induced-organisation-of-siedleckia-nematoides-cytoskeletal-elements
#4
Andrea Valigurová, Naděžda Vaškovicová, Andrei Diakin, Gita G Paskerova, Timur G Simdyanov, Magdaléna Kováčiková
Recent studies on motility of Apicomplexa concur with the so-called glideosome concept applied for apicomplexan zoites, describing a unique mechanism of substrate-dependent gliding motility facilitated by a conserved form of actomyosin motor and subpellicular microtubules. In contrast, the gregarines and blastogregarines exhibit different modes and mechanisms of motility, correlating with diverse modifications of their cortex. This study focuses on the motility and cytoskeleton of the blastogregarine Siedleckia nematoides Caullery et Mesnil, 1898 parasitising the polychaete Scoloplos cf...
2017: PloS One
https://www.readbyqxmd.com/read/28640848/easy-labeling-of-proliferative-phase-and-sporogonic-phase-of-microsporidia-nosema-bombycis-in-host-cells
#5
Jie Chen, Wei Guo, Xiaoqun Dang, Yukang Huang, Fangyan Liu, Xianzhi Meng, Yaoyao An, Mengxian Long, Jialing Bao, Zeyang Zhou, Zhonghuai Xiang, Guoqing Pan
Microsporidia are eukaryotic, unicellular parasites that have been studied for more than 150 years. These organisms are extraordinary in their ability to invade a wide range of hosts including vertebrates and invertebrates, such as human and commercially important animals. A lack of appropriate labeling methods has limited the research of the cell cycle and protein locations in intracellular stages. In this report, an easy fluorescent labeling method has been developed to mark the proliferative and sporogonic phases of microsporidia Nosema bombycis in host cells...
2017: PloS One
https://www.readbyqxmd.com/read/28640209/quinolin-6-yloxyacetamides-are-microtubule-destabilizing-agents-that-bind-to-the-colchicine-site-of-tubulin
#6
Ashwani Sharma, Gonzalo Sáez-Calvo, Natacha Olieric, Francisco de Asís Balaguer, Isabel Barasoain, Clemens Lamberth, J Fernando Díaz, Michel O Steinmetz
Quinolin-6-yloxyacetamides (QAs) are a chemical class of tubulin polymerization inhibitors that were initially identified as fungicides. Here, we report that QAs are potent anti-proliferative agents against human cancer cells including ones that are drug-resistant. QAs act by disrupting the microtubule cytoskeleton and by causing severe mitotic defects. We further demonstrate that QAs inhibit tubulin polymerization in vitro. The high resolution crystal structure of the tubulin-QA complex revealed that QAs bind to the colchicine site on tubulin, which is targeted by microtubule-destabilizing agents such as colchicine and nocodazole...
June 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28637765/electrostatic-interaction-between-polyglutamylated-tubulin-and-the-nexin-dynein-regulatory-complex-regulates-flagellar-motility
#7
Tomohiro Kubo, Toshiyuki Oda
Tubulins undergo various posttranslational modifications. Among them, polyglutamylation is involved in the motility of eukaryotic flagella and the stability of the axonemal microtubules. However, it remains unclear where polyglutamylated tubulin localizes precisely within the axoneme, and how tubulin polyglutamylation affects the flagellar motility. In this study, we identified the three-dimensional (3D) localization of the polyglutamylated tubulin in Chlamydomonas flagella using antibody labeling and cryo-electron tomography...
June 21, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28636913/heterogeneous-tau-tubulin-complexes-accelerate-microtubule-polymerization
#8
Xiao-Han Li, Elizabeth Rhoades
Tau is an intrinsically disordered protein with a central role in the pathology of a number of neurodegenerative diseases. Tau normally functions to stabilize neuronal microtubules, although the mechanism underlying this function is not well understood. Of note is that the interaction between tau and soluble tubulin, which has implications both in understanding tau function as well as its role in disease, is underexplored. Here we investigate the relationship between heterogeneity in tau-tubulin complexes and tau function...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28636161/infinity-sperm-storage-the-gift-that-keeps-on-giving
#9
Gauthier Schang, Beatriz Fernandez-Fuertes, Samantha C Lean, Alexandra L Nguyen, Osvaldo Bogado Pascottini
Female Drosophila retain sperm for up to two weeks post-copulation in a network of storage organs includng the bursa, the seminal receptacle, and the spermathecae. This image shows the seminal receptacle of a Drosophila melanogaster female, 2-hrs post-copulation between a LHM (wild-type) female with a Protamine B (green), β-Tubulin (blue) fluorescently tagged male, whose sperm can be visualized within the female. This 'infinity' structure of the seminal receptacle resembles the tubular coil that allows for the storage of very long sperm relative to female body size -up to 20 times the length of the female in some Drosophila species...
June 21, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28634443/the-narrow-abdomen-ion-channel-complex-is-highly-stable-and-persists-from-development-into-adult-stages-to-promote-behavioral-rhythmicity
#10
Devon L Moose, Stephanie J Haase, Benjamin T Aldrich, Bridget C Lear
The sodium leak channel NARROW ABDOMEN (NA)/ NALCN is an important component of circadian pacemaker neuronal output. In Drosophila, rhythmic expression of the NA channel regulator Nlf-1 in a subset of adult pacemaker neurons has been proposed to contribute to circadian regulation of channel localization or activity. Here we have restricted expression of Drosophila NA channel subunits or the Nlf-1 regulator to either development or adulthood using the temperature-inducible tubulin-GAL80(ts) system. Surprisingly, we find that developmental expression of endogenous channel subunits and Nlf-1 is sufficient to promote robust rhythmic behavior in adults...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28634388/mito-xenophagic-killing-of-bacteria-is-coordinated-by-a-metabolic-switch-in-dendritic-cells
#11
Nadine Radomski, Danny Kägebein, Elisabeth Liebler-Tenorio, Axel Karger, Elke Rufer, Birke Andrea Tews, Stefanie Nagel, Rebekka Einenkel, Anne Müller, Annica Rebbig, Michael R Knittler
Chlamydiae are bacterial pathogens that grow in vacuolar inclusions. Dendritic cells (DCs) disintegrate these compartments, thereby eliminating the microbes, through auto/xenophagy, which also promotes chlamydial antigen presentation via MHC I. Here, we show that TNF-α controls this pathway by driving cytosolic phospholipase (cPLA)2-mediated arachidonic acid (AA) production. AA then impairs mitochondrial function, which disturbs the development and integrity of these energy-dependent parasitic inclusions, while a simultaneous metabolic switch towards aerobic glycolysis promotes DC survival...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634179/lessons-from-bacterial-homolog-of-tubulin-ftsz-for-microtubule-dynamics
#12
Rachana Rao Battaje, Dulal Panda
FtsZ, a homolog of tubulin, is found in almost all bacteria and archaea where it has a primary role in cytokinesis. Evidence for structural homology between FtsZ and tubulin came from their crystal structures and identification of the GTP-box. Tubulin and FtsZ constitute a distinct family of GTPases and show striking similarities in many of their polymerization properties. The differences between them, more so, the complexities of microtubule dynamic behavior in comparison to that of FtsZ, indicate that the evolution to tubulin is attributable to the incorporation of the complex functionalities in higher organisms...
June 20, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28633670/preclinical-anti-myeloma-activity-of-edo-s101-a-new-bendamustine-derived-molecule-with-added-hdaci-activity-through-potent-dna-damage-induction-and-impairment-of-dna-repair
#13
Ana-Alicia López-Iglesias, Ana B Herrero, Marta Chesi, Laura San-Segundo, Lorena González-Méndez, Susana Hernández-García, Irena Misiewicz-Krzeminska, Dalia Quwaider, Montserrat Martín-Sánchez, Daniel Primo, Teresa Paíno, P Leif Bergsagel, Thomas Mehrling, Marcos González-Díaz, Jesús F San-Miguel, María-Victoria Mateos, Norma C Gutiérrez, Mercedes Garayoa, Enrique M Ocio
BACKGROUND: Despite recent advances in the treatment of multiple myeloma (MM), the prognosis of most patients remains poor, and resistance to traditional and new drugs frequently occurs. EDO-S101 is a novel therapeutic agent conceived as the fusion of a histone deacetylase inhibitor radical to bendamustine, with the aim of potentiating its alkylating activity. METHODS: The efficacy of EDO-S101 was evaluated in vitro, ex vivo and in vivo, alone, and in combination with standard anti-myeloma agents...
June 20, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28632973/molecular-modeling-study-on-the-tubulin-binding-modes-of-epothilone-derivatives-insight-into-the-structural-basis-for-epothilones-activity
#14
Verónica A Jiménez, Joel B Alderete, Karen R Navarrete
Molecular dynamics (MD) simulations were employed to study the tubulin-binding modes of 20 epothilone derivatives spanning a wide range of antitumor activity. Trajectory analysis revealed that active ligands shared a common region of association and similar binding poses compared to the high-resolution crystal structure of the tubulin complex with epothilone A, the stathmin-like protein RB3, and tubulin tyrosine ligase (PDB code 4I50). Conformational analysis of epothilones in aqueous solution and tubulin-bound states indicated that the bound conformations of active species can be found to a significant extent within the ensemble of conformers available in aqueous solution...
June 20, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28632150/centrosomal-protein-70-is-a-mediator-of-paclitaxel-sensitivity
#15
Xingjuan Shi, Yujue Wang, Xiaoou Sun, Chan Wang, Peng Jiang, Yu Zhang, Qinghai Huang, Xiangdong Liu, Dengwen Li, Jun Zhou, Min Liu
Centrosome aberrations have been implicated in the development and progression of breast cancer. Our previous worked show that centrosomal protein 70 (Cep70) regulates breast cancer growth and metastasis. However, it remains elusive whether Cep70 is implicated in the sensitivity of the anti-microtubule drug paclitaxel in breast cancer. Here we provide evidence that Cep70 is a mediator of paclitaxel sensitivity in breast cancer. Cell proliferation assays show that Cep70 expression correlates with paclitaxel sensitivity in breast cancer cell lines...
June 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28628789/challenges-and-opportunities-in-the-high-resolution-cryo-em-visualization-of-microtubules-and-their-binding-partners
#16
REVIEW
Eva Nogales, Elizabeth H Kellogg
As non-crystallizable polymers, microtubules have been the target of cryo-electron microscopy (cryo-EM) studies since the technique was first established. Over the years, image processing strategies have been developed that take care of the unique, pseudo-helical symmetry of the microtubule. With recent progress in data quality and data processing, cryo-EM reconstructions are now reaching resolutions that allow the generation of atomic models of microtubules and the factors that bind them. These include cellular partners that contribute to microtubule cellular functions, or small ligands that interfere with those functions in the treatment of cancer...
June 16, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28628007/direct-measurement-of-conformational-strain-energy-in-protofilaments-curling-outward-from-disassembling-microtubule-tips
#17
Jonathan W Driver, Elisabeth A Geyer, Megan E Bailey, Luke M Rice, Charles L Asbury
Disassembling microtubules can generate movement independently of motor enzymes, especially at kinetochores where they drive chromosome motility. A popular explanation is the 'conformational wave' model, in which protofilaments pull on the kinetochore as they curl outward from a disassembling tip. But whether protofilaments can work efficiently via this spring-like mechanism has been unclear. By modifying a previous assay to use recombinant tubulin and feedback-controlled laser trapping, we directly demonstrate the spring-like elasticity of curling protofilaments...
June 19, 2017: ELife
https://www.readbyqxmd.com/read/28626498/tubulin-beta-3-chain-as-a-new-candidate-protein-biomarker-of-human-skin-aging-a-preliminary-study
#18
Sylvia G Lehmann, Sandrine Bourgoin-Voillard, Michel Seve, Walid Rachidi
Skin aging is a complex process, and a lot of efforts have been made to identify new and specific targets that could help to diagnose, prevent, and treat skin aging. Several studies concerning skin aging have analyzed the changes in gene expression, and very few investigations have been performed at the protein level. Moreover, none of these proteomic studies has used a global quantitative labeled proteomic offgel approach that allows a more accurate description of aging phenotype. We applied such an approach on human primary keratinocytes obtained from sun-nonexposed skin biopsies of young and elderly women...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28626446/gnrh-induces-erk-dependent-bleb-formation-in-gonadotrope-cells-involving-recruitment-of-members-of-a-gnrh-receptor-associated-signalosome-to-the-blebs
#19
Liat Rahamim-Ben Navi, Anna Tsukerman, Alona Feldman, Philippa Melamed, Melanija Tomić, Stanko S Stojilkovic, Ulrich Boehm, Rony Seger, Zvi Naor
We have previously described a signaling complex (signalosome) associated with the GnRH receptor (GnRHR). We now report that GnRH induces bleb formation in the gonadotrope-derived LβT2 cells. The blebs appear within ~2 min at a turnover rate of ~2-3 blebs/min and last for at least 90 min. Formation of the blebs requires active ERK1/2 and RhoA-ROCK but not active c-Src. Although the following ligands stimulate ERK1/2 in LβT2 cells: EGF > GnRH > PMA > cyclic adenosine monophosphate (cAMP), they produced little or no effect on bleb formation as compared to the robust effect of GnRH (GnRH > PMA > cAMP > EGF), indicating that ERK1/2 is required but not sufficient for bleb formation possibly due to compartmentalization...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28624703/modification-of-c-seco-taxoids-through-ring-tethering-and-substituent-replacement-leading-to-effective-agents-against-tumor-drug-resistance-mediated-by-%C3%AE-iii-tubulin-and-p-glycoprotein-p-gp-overexpressions
#20
Yong Tang, Javier Rodríguez-Salarichs, Yu Zhao, Pei Cai, Juan Estévez-Gallego, Francisco Balaguer-Pérez, Mariano Redondo Horcajo, Daniel Lucena-Agell, Isabel Barasoain, J Fernando Díaz, Wei-Shuo Fang
In our efforts to improve the efficacy of taxane-based microtubule (MT) stabilizing agents against tumor drug resistance mediated by multiple mechanisms, two clinically relevant factors were focused: i.e., P-glycoprotein and βIII-tubulin overexpression. Based on the structure of C-seco taxoid 1 m (IDN5390) which was believed to more selectively interact with βIII-tubulin than paclitaxel, we prepared a series of C-seco taxoids bearing various 7,9-O-linkages and/or different substituents at C2 and C3' positions...
June 3, 2017: European Journal of Medicinal Chemistry
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